CN120476119A

CN120476119A - Microbicidal heterobicyclic dihydrooxadiazine derivatives

Info

Publication number: CN120476119A
Application number: CN202380075367.7A
Authority: CN
Inventors: N·吉尔曼; A·马哈詹; J·P·基拉鲁; T·J·霍夫曼
Original assignee: Syngenta Crop Protection AG Switzerland
Current assignee: Syngenta Crop Protection AG Switzerland
Priority date: 2022-10-27
Filing date: 2023-10-26
Publication date: 2025-08-12
Also published as: EP4608836A1; WO2024089191A1

Abstract

A compound of formula (I) wherein Q ^a or Q ^b is N, the other is C, Q ^c is N or CH, one or both of Q ⁷、Q⁸ and Q ⁹ is N, the other or both are CR ⁷、CR⁸ and CR ⁹ respectively, and the other substituents are as defined in claim 1, which is useful as a pesticide, in particular as a fungicide.

Description

Microbiocidal heterobicyclic dihydro-oxadiazine derivatives

The present invention relates to unsaturated N-bridged bicyclic heterocyclic derivatives as active ingredients, which have microbiocidal activity, and in particular fungicidal activity. The invention also relates to agrochemical compositions comprising at least one of the 5, 6-dihydro-4H-1, 2, 4-oxadiazine derivatives, to processes for the preparation of these compounds, and to the use of the 5, 6-dihydro-4H-1, 2, 4-oxadiazine derivatives or compositions in agriculture or horticulture for controlling or preventing infestation of plants, harvested food crops, seeds or non-living materials by phytopathogenic microorganisms, preferably fungi.

Many plant protection compounds have been developed to prevent or reduce plant diseases caused by microorganisms (e.g., fungi). For example, WO 2020/127780 discloses azabicyclo (thio) amides as fungicidal compounds and WO 2021/249995 discloses azabicyclo-substituted heterocycles as fungicides. The azabicyclic compounds disclosed therein are C-bridged and the monocyclic compounds are different isomers.

Accordingly, the present invention provides in a first aspect a compound having formula (I)

Or an agrochemically acceptable salt, stereoisomer, enantiomer, and N-oxide of the compound having formula (I), wherein:

Q ^a is N, Q ^b is C, and Q ^c is CH, or Q ^a is C, Q ^b is N, and Q ^c is N or CH;

Q ⁷ is N or C-R ⁷,Q⁸ is N or C-R ⁸ and Q ⁹ is N or C-R ⁹, wherein one or both of Q ⁷、Q⁸ and Q ⁹ are N, provided that when Q ^a is N, Q ⁷ and Q ⁸ are not both N;

R ¹ is phenyl optionally substituted with 1, 2 or 3 independently selected substituents R ¹¹, or

R ¹ is a 5-or 6-membered monocyclic heteroaryl ring containing 1, 2 or 3 heteroatoms each independently selected from N, O and S, wherein the heteroaryl ring is optionally substituted with 1 or 2 independently selected substituents R ¹¹;

R ¹¹ is hydroxy, halogen, mercapto, amino, cyano, methyl, ethyl, propyl, isopropyl, vinyl, ethynyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, allyloxy, prop-2-ynyloxy, prop-1-ynyloxy, methylsulfanyl, methylsulfonyl, difluoromethoxy, trifluoromethoxy, cyclopropyl, cyclobutyl, or cyclopropyloxy;

g is selected from the group consisting of G-1, G-2, G-3, and G-4, wherein:

g-1 is phenyl or phenoxy, wherein the phenyl or phenoxy is optionally substituted with 1,2 or 3 independently selected substituents R ^G1;

g-2 is a 5-or 6-membered monocyclic heteroaryl or heteroaryl-oxy group, wherein the heteroaryl group comprises 1, 2 or 3 heteroatoms each independently selected from N, O and S, and wherein the heteroaryl group is optionally substituted with 1 or 2 independently selected substituents R ^G2;

G-3 is a 9-or 10-membered heterobicyclic system comprising 1, 2, or 3 heteroatoms each independently selected from N, O and S, wherein the heterobicyclic system is saturated, partially unsaturated, or aromatic, and wherein the heterobicyclic system is optionally substituted with 1 or 2 independently selected substituents R ^G3;

g-4 is a 9-or 10-membered carbobicyclo system, wherein the carbobicyclo system is saturated, partially unsaturated, or aromatic, and wherein the carbobicyclo system is optionally substituted with 1 or 2 independently selected substituents R ^G4;

R ^G1、R^G2、R^G3, and R ^G4 are independently hydroxy, halogen, mercapto, amino, cyano, C _1-4 alkyl, vinyl, ethynyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, allyloxy, prop-2-ynyloxy, prop-1-ynyloxy, methylsulfanyl, methylsulfonyl, difluoromethoxy, trifluoromethoxy, cyclopropyl, cyclobutyl, or cyclopropyloxy;

R ⁷、R⁸, and R ⁹ are independently selected from hydrogen, fluoro, chloro, bromo, iodo, C _1-4 alkyl, allyl, propargyl, cyclopropylmethyl, cyclopentyl, cyclohexyl, -C (=O) OCH ₃、-C(＝O)N(CH₃)₂, 2- (dimethylamino) -2-oxo-ethyl, 2- (methylamino) -2-oxo-ethyl, difluoromethyl, trifluoromethyl, methylsulfonyl, methylsulfanyl, methoxy, ethoxy, cyano, hydroxy, mercapto, and amino.

The invention also provides a process for preparing compounds having formula (I) and intermediate compounds useful in preparing compounds having formula (I).

Surprisingly, it has been found that for practical purposes the novel compounds of formula (I) have a very advantageous level of biological activity for protecting plants against diseases caused by fungi.

According to a second aspect of the present invention there is provided an agrochemical composition comprising a fungicidally effective amount of a compound of formula (I). Such agricultural compositions may further comprise at least one additional active ingredient and/or an agrochemically acceptable diluent or carrier.

According to a third aspect of the present invention there is provided a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a fungicidally effective amount of a compound of formula (I), or a composition comprising such a compound as active ingredient, is applied to the plants, parts thereof or the locus thereof.

According to a fourth aspect of the present invention there is provided the use of a compound of formula (I) as a fungicide. According to this particular aspect of the invention, the use may not include methods of treating the human or animal body by surgery or therapy.

According to a fifth aspect, the present invention makes it possible to obtain a plant propagation material, such as a seed, containing a compound of formula (I) or a composition comprising such a compound, or treated with the compound or the composition, or having the compound or the composition adhered thereto.

As used herein, the term "hydroxyl" or "hydroxyl" means an-OH group.

As used herein, the term "mercapto" means a —sh group.

As used herein, the term "cyano" means a —cn group.

As used herein, amino means the —nh ₂ group.

As used herein, nitro means a-NO ₂ group.

As used herein, oxo means an =o group (e.g., as in a carbonyl (c=o) group).

As used herein, the term "halogen" or "halo" refers to fluorine (fluoro), chlorine (chloro), bromine (bromine, bromo) or iodine (iodine, iodo), preferably fluorine, chlorine or bromine. This applies correspondingly to halogens, such as haloalkyl, in combination with other meanings.

As used herein, the term "C _1-4 alkyl" refers to a straight or branched hydrocarbon chain group consisting of only carbon and hydrogen atoms, which is free of unsaturation, has from one to four carbon atoms, and is attached to the remainder of the molecule by a single bond. C _1-3 alkyl should be construed accordingly. Examples of C _1-4 alkyl groups include, but are not limited to, methyl, ethyl, isopropyl.

As used herein, the term "C _2-3 alkenyl" refers to a straight or branched hydrocarbon chain group consisting of only carbon and hydrogen atoms, containing at least one double bond that may have the (E) or (Z) configuration, with two or three carbon atoms, attached to the remainder of the molecule by single bonds. Examples of C _2-3 alkenyl include, but are not limited to, vinyl (vinyl or ethenyl), prop-1-enyl, allyl (prop-2-enyl).

As used herein, the term "C _2-3 alkynyl" refers to a straight or branched hydrocarbon chain group consisting of only carbon and hydrogen atoms, containing at least one triple bond, having two or three carbon atoms, and attached to the remainder of the molecule by single bonds. Examples of C _2-3 alkynyl include, but are not limited to, prop-1-ynyl and propargyl (prop-2-ynyl).

As used herein, the terms "C _1-4 haloalkyl", "C _2-3 haloalkenyl", and "C _2-3 haloalkynyl" refer to C _1-4 alkyl, C _2-3 alkenyl, and C _2-3 alkynyl groups, respectively, as defined above, substituted with one or more identical or different halogen atoms. Examples of C _1-4 haloalkyl include, but are not limited to, fluoromethyl, fluoroethyl, difluoromethyl, trifluoromethyl, and 2, 2-trifluoroethyl.

As used herein, the term "C _1-3 fluoroalkyl" refers to a C _1-3 alkyl group as generally defined above substituted with one or more fluorine atoms. Examples of C _1-3 fluoroalkyl groups include, but are not limited to, difluoromethyl and trifluoromethyl.

As used herein, the term "C _1-3 alkoxy" refers to a group having the formula R _a O-, wherein R _a is a C _1-3 alkyl group as generally defined above. Examples of C _1-3 alkoxy groups include, but are not limited to, methoxy, ethoxy, isopropoxy.

As used herein, the term "C _1-3 fluoroalkoxy" refers to a C _1-3 alkoxy group as generally defined above substituted with one or more fluorine atoms. Examples of C _1-3 fluoroalkoxy groups include, but are not limited to, trifluoromethoxy.

As used herein, the term "C _3-4 cycloalkyl" refers to a stable monocyclic group that is saturated and contains 3 or 4 carbon atoms.

As used herein, the term "C _1-3 alkylsulfanyl" refers to a group having the formula-SR _a, wherein R _a is a C _1-3 alkyl group as generally defined above.

As used herein, the term "C _1-3 alkylsulfonyl" refers to a group having the formula-S (O) ₂R_a, wherein R _a is a C _1-3 alkyl group as generally defined above.

As used herein, the term "heteroaryl" refers to a 5-or 6-membered aromatic monocyclic ring having 1 to 3 heteroatoms independently selected from N, O and S. Examples of heteroaryl groups include J-1 to J-41 shown in Table J below. The alternate lines in heteroaryl J-1 through J-43 represent points of attachment to the remainder of the compound. Preferred heteroaryl groups include pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, and thiazolyl, preferably pyridyl and thiazolyl.

Heteroaryl groups J-1 to J-43:

As used herein, the term "heterocyclyl" refers to 3-, 4-, 5-, and 6-membered saturated monocyclic rings having 1 or 2 heteroatoms independently selected from nitrogen and oxygen. Examples of the heterocyclic groups include K-1 to K-26 shown in the following Table K. The alternate lines in heterocyclyl groups K-1 through K-26 represent points of attachment to the remainder of the compound. Some of the heterocyclic groups shown below contain asymmetric carbons, which means that the compounds containing them can exist in chiral isomer form, i.e. in enantiomeric or diastereoisomeric form. Preferred heterocyclyl groups include pyrrolidinyl, piperidinyl, piperazinyl, and tetrahydropyranyl, with pyrrolidinyl, piperazinyl, and tetrahydropyranyl being preferred.

Table K heterocyclic groups K-1 to K-26:

As used herein, the term "optionally substituted" means that the referenced group is unsubstituted or substituted with a specified substituent, e.g., "C ₃-C₄ cycloalkyl optionally substituted with 1 or 2 halo atoms" means C ₃-C₄ cycloalkyl, C ₃-C₄ cycloalkyl substituted with 1 halo atom, and C ₃-C₄ cycloalkyl substituted with 2 halo atoms.

The staggered lines as used herein, e.g., in heteroaryl groups shown in table J and heterocyclyl groups shown in table K, represent points of attachment to the rest of the compound.

The presence of one or more possible asymmetric carbon atoms in the compounds of formula (I) means that these compounds can exist in chiral isomeric forms, i.e. in enantiomeric or diastereoisomeric forms. Also, as a result of limited rotation around a single bond, atropisomers may be present. Formula (I) is intended to include all those possible isomeric forms and mixtures thereof. The present invention includes all those possible isomeric forms of the compounds having formula (I) and mixtures thereof. Likewise, formula (I) is intended to include all possible tautomers (including lactam-lactam tautomers and keto-enol tautomers), when present. The present invention includes all possible tautomeric forms of the compounds having formula (I).

The compounds of formula (I) having at least one basic center may for example form acid addition salts with strong mineral acids (such as mineral acids, for example perchloric acid, sulfuric acid, nitric acid, nitrous acid, phosphoric acid or hydrohalic acid), strong organic carboxylic acids (such as unsubstituted or for example halogen-substituted C ₁-C₄ -alkanecarboxylic acids, for example acetic acid, such as saturated or unsaturated dicarboxylic acids, for example oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid or phthalic acid, such as hydroxycarboxylic acids, for example ascorbic acid, lactic acid, malic acid, tartaric acid or citric acid, or such as benzoic acid), or organic sulfonic acids (such as unsubstituted or for example halogen-substituted C ₁-C₄ -alkanesulfonic acids or arylsulfonic acids, for example methanesulfonic acid or p-toluenesulfonic acid). The compounds of the formula (I) having at least one acidic group may for example form salts with bases, for example mineral salts, such as alkali metal or alkaline earth metal salts, for example sodium, potassium or magnesium salts, or with ammonia or organic amines, such as morpholine, piperidine, pyrrolidine, mono-, di-or tri-lower alkylamines, for example ethylamine, diethylamine, triethylamine or dimethylpropylamine, or mono-, di-or tri-hydroxy lower alkylamines, for example monoethanolamine, diethanolamine or triethanolamine.

The compounds of formula (I) according to the invention also include hydrates which can be formed during salt formation.

In each case, the compounds according to the invention of formula (I) are in free form, oxidized form (as N-oxide), covalently hydrated form, or in salt form (such as agronomically usable or agronomically acceptable salt form).

The N-oxide is an oxidized form of a tertiary amine or an oxidized form of a nitrogen-containing heteroaromatic compound. Albini and S.Pietra are described, for example, in the publication of Bokaraton (Boca Raton) CRC Press by A.Albini and S.Pietra under the name "Heterocholic N-oxides [ Heterocyclic N-oxides ]".

In the description, compounds having formula (I) may be represented by the following formula (Ia):

wherein A represents And

Wherein # denotes a bond to-O-R ¹ and% denotes a bond to the-5, 6-dihydro-4H-1, 2, 4-oxadiazin-3-yl-G moiety, and R ¹、Q^a、Q^b、Q^c、Q⁷、Q⁸、Q⁹, and G have the same meanings as given above for the compound having formula (I).

The definitions given for Q ^a、Q^b、Q^c、Q⁷、Q⁸, and Q ⁹ yield the following groups a-1 to a-17 defined in table 1 and shown in table 2:

TABLE 1 group A in which R ⁷、R⁸、R⁹ has the same meaning as in the compounds having (I)

A

Q^a

Q^b

Q^c

Q⁷

Q⁸

Q⁹

A-1

C

N

CH

N

CR⁸

CR⁹

A-2

C

N

CH

CR⁷

N

CR⁹

A-3

C

N

CH

CR⁷

CR⁸

N

A-4

C

N

CH

N

CR⁹

A-5

C

N

CH

N

CR⁸

N

A-6

C

N

CH

CR⁷

N

A-7

C

N

CR⁸

CR⁹

A-8

C

N

CR⁷

N

CR⁹

A-9

C

N

CR⁷

CR⁸

N

A-10

C

N

CR⁹

A-11

C

N

CR⁷

N

A-12

C

N

CR⁸

N

A-13

N

C

CH

N

CR⁸

CR⁹

A-14

N

C

CH

CR⁷

N

CR⁹

A-15

N

C

CH

CR⁷

CR⁸

N

A-16

N

C

CH

CR⁷

N

A-17

N

C

CH

N

CR⁸

N

Table 2-group A wherein # and% have the same meaning as in the compound having (Ia) and R ⁷、R⁸、R⁹ has the same meaning as in the compound having (I):

The following list provides definitions, including preferred definitions, of group a and substituents R¹、G、R¹⁰、R^10a、R^10b、R¹¹、R¹²、R^12a、R^12b、R^G1、R^G2、R^G3、 and R ^G4, with reference to the compounds of formula (I) of the present invention. For any of these groups or substituents, any of the definitions set forth below may be combined with any of the definitions of any other substituents set forth below or elsewhere in this document.

In embodiments of various aspects of the invention, a is selected from:

A.A-1, A-2, A-3, A-4, A-5, A-6, A-7, A-8, A-9, A-10, A-11, A-12, A-13, A-14, A-15, A-16 and A-17, or

B.A-1, A-2, A-3, A-4, A-5, A-6, A-7, A-8, A-9, A-10, A-11, and A-12, or

C.A-13, A-14, A-15, A-16, and A-17, or

D.A-1, A-2, A-3, A-4, A-5, and A-6, or

E.A-7, A-8, A-9, A-10, A-11, and A-12, or

F.A-13, A-14, A-15, A-16, and A-17, or

G.A-1, A-2, A-3, A-13, A-14, and A-15, or

H.A-4, A-5, A-6, A-7, A-8, A-9, A-15, A-16, and A-17, or

I.A-10, A-11, and A-12, or

J.A-1, A-2, A-3, A-4, A-5, A-7, A-8, A-9, A-10, A-12, A-14, A-15, and A-16;

K.A-1, A-2, A-3, A-4, A-5, A-7, A-8, A-9, A-14, A-15, and A-16;

L.A-1, A-2, A-3, A-7, A-8, A-9, A-13, A-14, and A-15, or

M.A-4, A-5, A-6, A-10, A-11, A-12, A-16, and A-17, or

N.A-1, A-2, A-3, A-5, A-9, A-14, and A-15, or

O.A-1, A-3, A-5 and A-15, or

P.A-1, A-3 and A-15, or

Q.A-3, A-5 and A-15.

In preferred embodiments of various aspects of the invention, A is selected from A-1, A-2, A-3, A-5, A-9, A-14, and A-15. In other words, Q ^a、Q^b、Q^c、Q⁷、Q⁸ and Q ⁹ are defined as follows:

A.Q ^a is C, Q ^b is N, Q ^c is CH, and a single one of Q ⁷、Q⁸ and Q ⁹ is N, or

Q ^a is C, Q ^b is N, Q ^c is CH, Q ⁷ is N or CR ⁷,Q⁸ is CR ⁸, and Q ⁹ is N, or

C.Q ^a is N, Q ^b is C, Q ^c is CH, Q ⁷ is CR ⁷, and a single one of Q ⁸ and Q ⁹ is N, or

D.Q ^a is C, Q ^b is N, Q ^c is CH, Q ⁷ is CR ⁷,Q⁸ is CR ⁸, and Q ⁹ is N, or

E.Q ^a is C, Q ^b is N, Q ^c is CH, Q ⁷ is N, Q ⁸ is CR ⁸, and Q ⁹ is N, or

F.Q ^a is N, Q ^b is C, Q ^c is CH, Q ⁷ is CR ⁷,Q⁸ is CR ⁸, and Q ⁹ is N.

In a more preferred embodiment of various aspects of the invention, A is selected from A-3, A-5, And A-15, i.e., Q ^a is C, Q ^b is N, Q ^c is CH, Q ⁷ is CR ⁷,Q⁸ is CR ⁸, and Q ⁹ is N, or Q ^a is C, Q ^b is N, Q ^c is CH, Q ⁷ is N, Q ⁸ is CR ⁸, and Q ⁹ is N, or Q ^a is N, Q ^b is C, Q ^c is CH, Q ⁷ is CR ⁷,Q⁸ is CR ⁸, and Q ⁹ is N.

In embodiments of various aspects of the invention, R ⁷、R⁸ and R ⁹, when present, are, independently of each other:

A. Hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, allyl, propargyl, cyclopropylmethyl, cyclopropyl, cyclopentyl, cyclohexyl, -C (=o) OCH ₃、-C(＝O)N(CH₃)₂, 2- (dimethylamino) -2-oxo-ethyl, 2- (methylamino) -2-oxo-ethyl, difluoromethyl, trifluoromethyl, methylsulfonyl, methylsulfanyl, thiomethoxy, methoxy, ethoxy, cyano, hydroxy, mercapto, and amino;

B. Hydrogen, fluorine, chlorine, methyl, ethyl, isopropyl, cyclopropyl, -C (=O) OCH ₃、-C(＝O)N(CH₃)₂, 2- (dimethylamino) -2-oxo-ethyl, 2- (methylamino) -2-oxo-ethyl, difluoromethyl, trifluoromethyl, methylsulfonyl, methoxy, or cyano, or

C. Hydrogen, fluoro, chloro, methyl, ethyl, cyclopropyl, 2- (methylamino) -2-oxo-ethyl, methylsulfonyl, methoxy, or cyano, or

D. Hydrogen, chlorine, fluorine, methyl, cyclopropyl, or cyano, or

E. Hydrogen, chlorine, fluorine, or methyl, or

F. hydrogen, chlorine, or fluorine, or

G.R ⁷ is hydrogen, chlorine, or methyl, R ⁸ is hydrogen, chlorine, fluorine, or methyl, R ⁹ is hydrogen or methyl, provided that when only one of Q ⁷、Q⁸ and Q ⁹ is nitrogen, at least one of R ⁷、R⁸ and R ⁹ is hydrogen, or

H.R ⁷ is hydrogen, chlorine, or methyl, R ⁸ is hydrogen, chlorine, or fluorine, R ⁹ is hydrogen or methyl, provided that when only one of Q ⁷、Q⁸ and Q ⁹ is nitrogen, at least one of R ⁷、R⁸ and R ⁹ is hydrogen, or

I. In the case where two of Q ⁷、Q⁸ and Q ⁹ are nitrogen, R ⁷ is hydrogen, chlorine or methyl, R ⁸ is hydrogen, chlorine, fluorine or methyl, R ⁹ is hydrogen or methyl;

J. In the case where two of Q ⁷、Q⁸ and Q ⁹ are nitrogen, R ⁷ and R ⁹ are hydrogen or methyl, and R ⁸ is hydrogen or fluorine.

In embodiments of various aspects of the invention, R ¹ is:

A. Phenyl optionally substituted with one, two or three independently selected substituents R ¹¹, e.g., one or two independently selected substituents R ¹¹, preferably one substituent R ¹¹, wherein R ¹¹ is selected from hydroxy, halo, mercapto, amino, cyano, methyl, ethyl, propyl, isopropyl, vinyl, ethynyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, allyloxy, prop-2-ynyloxy, prop-1-ynyloxy, methylsulfanyl, methylsulfonyl, difluoromethoxy, trifluoromethoxy, cyclopropyl, cyclobutyl, and cyclopropyloxy, or

B. Phenyl substituted with one or two substituents R ¹¹, e.g. one substituent R ¹¹, wherein R ¹¹ is selected from hydroxy, halogen, cyano, methyl, vinyl, ethynyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, allyloxy, propargyloxy, difluoromethoxy, trifluoromethoxy, cyclopropyl, and cyclobutyl, or

C. Phenyl substituted with one or two substituents independently selected from hydroxy, halogen, cyano, methyl, vinyl, ethynyl, methoxy, ethoxy, allyloxy, propargyloxy, difluoromethoxy, trifluoromethoxy, cyclopropyl, and cyclobutyl, e.g., one substituent, or

D. phenyl optionally substituted with one or two substituents independently selected from chloro, fluoro, cyano, methyl, methoxy, and cyclopropyl, e.g., one substituent, or

E. phenyl substituted by a single substituent selected from methyl and cyclopropyl, or

F. A 5-or 6-membered monocyclic heteroaryl ring containing 1, 2 or 3 heteroatoms, which may be the same or different, independently selected from N, O and S, wherein said heteroaryl ring is optionally substituted with 1 or 2 independently selected substituents R ¹¹, or

G. A 6 membered monocyclic heteroaryl ring containing 1,2 or 3 nitrogen atoms, wherein said heteroaryl ring is optionally substituted with 1 or 2 independently selected substituents R ¹¹, or

H. Pyridine, pyrimidine, pyridazine, or 1,2, 4-triazine, wherein the pyridine, pyrimidine, pyridazine, 1,2, 4-triazine is optionally substituted with one or two substituents independently selected from hydroxy, halogen, mercapto, amino, cyano, methyl, ethyl, propyl, isopropyl, vinyl, ethynyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, allyloxy, prop-2-ynyloxy, prop-1-ynyloxy, methylsulfanyl, methylsulfonyl, difluoromethoxy, trifluoromethoxy, cyclopropyl, cyclobutyl, and cyclopropyloxy, or

I. Pyridine substituted with one or two substituents independently selected from hydroxy, halogen, cyano, methyl, vinyl, ethynyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, allyloxy, propargyloxy, difluoromethoxy, trifluoromethoxy, cyclopropyl, and cyclobutyl, or

J. Pyridine substituted with a single substituent selected from chloro, fluoro, cyano, methyl, methoxy, difluoromethoxy, and cyclopropyl, or

K. Pyridine substituted with a single substituent selected from chlorine, cyano, and methyl, or

L, phenyl, pyridinyl, pyrimidinyl, or pyridazinyl, each optionally substituted with one or two substituents R ¹¹ independently selected from hydroxy, halo, mercapto, amino, cyano, methyl, ethyl, propyl, isopropyl, vinyl, ethynyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, allyloxy, prop-2-ynyloxy, prop-1-ynyloxy, methylsulfanyl, methylsulfonyl, difluoromethoxy, trifluoromethoxy, cyclopropyl, cyclobutyl, and cyclopropyloxy, or

M, phenyl, pyridinyl, or pyrimidinyl, each optionally substituted with one or two substituents R ¹¹ independently selected from hydroxy, halo, cyano, methyl, vinyl, ethynyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, allyloxy, propargyloxy, difluoromethoxy, trifluoromethoxy, cyclopropyl, and cyclobutyl, or

N, phenyl, or pyridinyl, each optionally substituted with one or two substituents R ¹¹ independently selected from hydroxy, halogen, cyano, methyl, vinyl, ethynyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, allyloxy, propargyloxy, difluoromethoxy, trifluoromethoxy, cyclopropyl, and cyclobutyl, or

O, phenyl, or pyridinyl, each optionally substituted with one or two substituents R ¹¹ independently selected from chloro, fluoro, cyano, methyl, methoxy, difluoromethoxy, and cyclopropyl, or

P, phenyl, or pyridinyl, each optionally substituted with one or two substituents R ¹¹ independently selected from chloro, cyano, methyl, trifluoromethyl, ethynyl, and cyclopropyl, or

Q, phenyl, or pyridinyl, each optionally substituted with one or two substituents R ¹¹ independently selected from chloro, methyl, cyano, and cyclopropyl, or

R, phenyl, or phenyl substituted with a single substituent selected from methyl, trifluoromethyl, ethynyl, chloro and cyclopropyl, or 3-cyclopropyl-2-fluorophenyl, or pyridyl substituted with a single substituent selected from cyano and cyclopropyl, or

S.3-cyclopropyl-2-fluorophenyl, 3- (trifluoromethyl) phenyl, 3-ethynylphenyl, 3-chlorophenyl, 5-cyanopyridin-3-yl, 5- (cyclopropyl) pyridin-3-yl, 3-phenyl, 3-tolyl, or 3-cyclopropylphenyl, or

T.3-cyclopropylphenyl.

In embodiments of various aspects of the invention, R ¹¹ is:

A. Hydroxy, halogen, mercapto, amino, cyano, methyl, ethyl, propyl, isopropyl, vinyl, ethynyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, allyloxy, prop-2-ynyloxy, prop-1-ynyloxy, methylsulfanyl, methylsulfonyl, difluoromethoxy, trifluoromethoxy, cyclopropyl, cyclobutyl, and cyclopropyloxy, or

B. Hydroxy, halogen, cyano, methyl, vinyl, ethynyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, allyloxy, propargyloxy, difluoromethoxy, trifluoromethoxy, cyclopropyl, and cyclobutyl, or

C. Hydroxy, cyano, methyl, vinyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, allyloxy, propargyloxy, difluoromethoxy, trifluoromethoxy, cyclopropyl, and cyclobutyl, or

D. Halogen, cyano, methyl, ethynyl, difluoromethyl, trifluoromethyl, methoxy, allyloxy, difluoromethoxy, trifluoromethoxy, and cyclopropyl, or

E. cyano, methyl, methoxy, allyloxy, trifluoromethoxy, cyclopropyl, and cyclobutyl, or

F. chloro, fluoro, cyano, methoxy, allyloxy, trifluoromethoxy, cyclopropyl, and cyclobutyl, or

G. Halogen, cyano, methoxy, allyloxy, trifluoromethoxy, and cyclopropyl, or

H. chloro, fluoro, cyano, cyclopropyl and cyclobutyl, or

I. chloro, fluoro, cyano, methyl, cyclopropyl, trifluoromethyl, ethynyl, or

I. Chloro, cyano, cyclopropyl and methyl, or

J. And (3) cyclopropyl.

In embodiments of various aspects of the invention, G is:

A. Phenyl optionally substituted with one or two substituents independently selected from hydroxy, halogen, mercapto, amino, cyano, methyl, ethyl, propyl, isopropyl, vinyl, ethynyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, allyloxy, prop-2-ynyloxy, prop-1-ynyloxy, methylsulfanyl, methylsulfonyl, difluoromethoxy, trifluoromethoxy, cyclopropyl, cyclobutyl, or cyclopropyloxy, or

B. Phenyl optionally substituted with one or two substituents independently selected from hydroxy, halogen, cyano, methyl, vinyl, ethynyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, allyloxy, propargyloxy, difluoromethoxy, trifluoromethoxy, cyclopropyl, and cyclobutyl, or

C. Phenyl optionally substituted with 1, 2 or 3 substituents, e.g., 2 or 3 substituents, each independently selected from chloro, fluoro, methyl, and methoxy, or

D. phenyl substituted by one or two substituents selected from chloro and methyl, e.g. one substituent, or

E. Pyridine, pyrimidine, pyridazine, or 1,2, 4-triazine, wherein the pyridine, pyrimidine, pyridazine, 1,2, 4-triazine is optionally substituted with one or two substituents independently selected from hydroxy, halogen, mercapto, amino, cyano, methyl, ethyl, propyl, isopropyl, vinyl, ethynyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, allyloxy, prop-2-ynyloxy, prop-1-ynyloxy, methylsulfanyl, methylsulfonyl, difluoromethoxy, trifluoromethoxy, cyclopropyl, cyclobutyl, and cyclopropyloxy, or

F. Pyridine, pyrimidine, or pyridazine substituted with one or two substituents independently selected from hydroxy, halogen, cyano, methyl, vinyl, ethynyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, allyloxy, propargyloxy, difluoromethoxy, trifluoromethoxy, cyclopropyl, and cyclobutyl, or

G. pyrimidine or pyridazine substituted with one or two substituents independently selected from hydroxy, halogen, cyano, methyl, vinyl, ethynyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, allyloxy, propargyloxy, difluoromethoxy, trifluoromethoxy, cyclopropyl, and cyclobutyl, or

H. pyridine substituted with 1, 2 or 3 substituents, e.g., 2 or 3 substituents, each independently selected from chloro, fluoro, cyano, methyl, and methoxy, or

I. pyridine substituted by one or two substituents selected from chlorine and methyl, e.g. one substituent, or

J. chroman-4-yl, isochroman-4-yl, 4H-chromen-4-yl, 2, 3-dihydrobenzofuran-2-yl, 2, 3-dihydrobenzofuran-3-yl, 1, 3-benzodioxol-5-yl, benzothiazol-2-yl, benzothiazol-5-yl, benzothiazol-6-yl, benzoxazol-2-yl, benzoxazol-5-yl, benzoxazol-6-yl, benzofuran-2-yl, benzofuran-3-yl, benzofuran-5-yl, benzofuran-6-yl, benzothien-2-yl, benzothien-3-yl, benzothien-5-yl, benzothien-6-yl, or

K. Chroman-4-yl, isochroman-4-yl, 4H-chromen-4-yl, 2, 3-dihydrobenzofuran-2-yl, 2, 3-dihydrobenzofuran-3-yl, 1, 3-benzodioxol-5-yl, benzothiazol-2-yl, benzothiazol-5-yl, benzothiazol-6-yl, benzoxazol-2-yl, benzofuran-3-yl, or benzothien-2-yl, benzothien-3-yl substituted with one substituent selected from chloro, fluoro, cyano, methyl, and methoxy;

L. chroman-4-yl, isochroman-4-yl, 4H-chromen-4-yl, 2, 3-dihydrobenzofuran-2-yl, or 2, 3-dihydrobenzofuran-3-yl substituted with one substituent selected from chloro, fluoro, cyano, methyl, and methoxy, or

M.1, 3-Benzodioxol-5-yl, benzothiazol-2-yl, benzothiazol-5-yl, benzothiazol-6-yl, benzoxazol-2-yl, benzofuran-3-yl, benzothien-2-yl, or benzothien-3-yl, or

N. naphthalen-2-yl, tetralin-1-yl, tetralin-2-yl, tetralin-6-yl, indan-1-yl, indan-2-yl, or indan-5-yl, optionally substituted with 1,2 or 3 substituents each independently selected from chloro, fluoro, cyano, methyl, and methoxy, e.g., one or two substituents

O. or optionally substituted with one or two substituents each independently selected from chloro, fluoro, cyano, methyl, and methoxy, e.g. one substituent, tetralin-1-yl, tetralin-2-yl, indan-1-yl, or indan-2-yl, or

P. tetralin-1-yl or indan-1-yl substituted with one substituent selected from chlorine, fluorine, cyano, methyl, and methoxy, or

Q.2, 4-dimethylphenyl, 2, 4-dichlorophenyl, 4-bromo-2-methylphenyl, 4-bromo-2-chlorophenyl, 2, 6-dichloro-3-pyridinyl, 4, 6-dichloro-3-pyridinyl, 3, 5-dichloro-2-pyridinyl, 3, 5-dichloro-thienyl, 3, 5-dimethyl-thienyl, 3, 4-dimethylphenyl, 2-chloro-4-methylphenyl, 2-bromo-4-chlorophenyl, 4-chloro-2-fluorophenyl, or 2-chloro-4-fluorophenyl; or

R.2, 4-dimethylphenyl, 2, 4-dichlorophenyl, 4-bromo-2-methylphenyl, 4-bromo-2-chlorophenyl, 3, 4-dimethylphenyl, 2-chloro-4-methylphenyl, 2-bromo-4-chlorophenyl, 4-chloro-2-fluorophenyl, or 2-chloro-4-fluorophenyl, or

S.2, 4-dichlorophenyl.

In embodiments of various aspects of the invention, R ^G1、R^G2、R^G3, and R ^G4 are independently selected from:

A. Hydroxy, halogen such as chloro and fluoro, mercapto, amino, cyano, methyl, ethyl, propyl, isopropyl, vinyl, ethynyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, allyloxy, prop-2-ynyloxy, prop-1-ynyloxy, methylsulfanyl, methylsulfonyl, difluoromethoxy, trifluoromethoxy, cyclopropyl, cyclobutyl, or cyclopropyloxy, or

C. Hydroxy, chloro, fluoro, cyano, methyl, vinyl, ethynyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, allyloxy, propargyloxy, difluoromethoxy, trifluoromethoxy, cyclopropyl, and cyclobutyl, or

D. chlorine, fluorine, cyano, methyl, and methoxy, or

E. Chlorine and methyl.

In one embodiment of the present invention, the compound having formula (I) according to the present invention is selected from the compounds listed in any one of tables A-1 to A-27.

Preferably, the compounds according to the invention having formula (I) are selected from the compounds as listed in table T1 (below).

Even more preferably, the compounds of formula (I) according to the invention are selected from

3- [6- (3-Cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidin-7-yl ] -5- [ (2, 4-dichlorophenyl) methyl ] -5, 6-dihydro-4H-1, 2, 4-oxadiazine,

3- [ 3-Chloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidin-7-yl ] -5- [ (2, 4-dichlorophenyl) methyl ] -5, 6-dihydro-4H-1, 2, 4-oxadiazine,

3- [6- (3-Cyclopropylphenoxy) -2-fluoro-pyrazolo [1,5-a ] pyrimidin-7-yl ] -5- [ (2, 4-dichlorophenyl) methyl ] -5, 6-dihydro-4H-1, 2, 4-oxadiazine,

3- [ 2-Chloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidin-7-yl ] -5- [ (2, 4-dichlorophenyl) methyl ] -5, 6-dihydro-4H-1, 2, 4-oxadiazine, or

3- [7- (3-Cyclopropylphenoxy) imidazo [1,2-b ] pyridazin-8-yl ] -5- [ (2, 4-dichlorophenyl) methyl ] -5, 6-dihydro-4H-1, 2, 4-oxadiazine.

Compounds having formula (I) comprise a stereogenic center, shown with asterisks in formulae (I) and (I) a), wherein A、G、Q^a、Q^b、Q^c、Q⁷、Q⁸、Q⁹、R¹、R⁷、R⁸、R⁹、 and R ¹¹ are as defined in the first aspect, each having the corresponding embodiments as described above.

The compounds of the invention may be enantiomers of compounds having formula (I) or (Ia), as represented by formula (I-R) or formula (I-S) or formula (Ia-R) or formula (Ia-S), wherein A、G、Q^a、Q^b、Q^c、Q⁷、Q⁸、Q⁹、R¹、R⁷、R⁸、R⁹、 and R ¹¹ are as defined in the first aspect.

The compounds of formula (I) may be prepared by one skilled in the art as shown in schemes 1 to 46 below, wherein G、Q^a、Q^b、Q^c、Q⁷、Q⁸、Q⁹、R¹、R⁷、R⁸、R⁹、 and R ¹¹ are as defined for compounds of formula (I) and a is as defined for compounds of formula (Ia) unless otherwise indicated. For clarity, in the intermediate compounds shown in schemes 1 to 46, a representsWherein # marks a bond to-O-R ¹ or a corresponding precursor group in an intermediate compound and% marks a bond to-5, 6-dihydro-4H-1, 2, 4-oxadiazin-3-yl-G moiety or a corresponding precursor group in an intermediate compound, and Q ^a、Q^b、Q^c、Q⁷、Q⁸, and Q ⁹ have the same meanings as given for the compound having formula (I). For clarity, certain stereogenic centers are not indicated and are not intended to limit the teachings of these schemes in any way.

As shown in scheme 1, compounds of formula (I) can be obtained by intramolecular cyclization of compounds of formula (II) in a suitable solvent or solvent mixture (e.g., dichloromethane, dimethylformamide, 2-methyltetrahydrofuran, tetrahydrofuran, diethyl ether, toluene, ethyl acetate) using a chlorinating agent, for example by using poci ₃、PCl₅、(COCl)₂ or SOCl ₂, optionally in the presence of dimethylformamide, preferably at a temperature between 0 ℃ and 80 ℃, more preferably between 25 ℃ and 60 ℃. See, e.g., heterocycles (2016), 92 (12), 2166-2200 or CN 114437077.

Scheme 1

As shown in scheme 2, compounds having formula (II) can be obtained by amine deprotection of compounds having formula (III) wherein X ¹ is H and X ² is a protecting group, or X ¹ and X ² are the same or different protecting groups, or X ¹ and X ² together with the nitrogen to which they are attached form a protecting group. Examples of protecting groups include, for example, t-butyloxycarbonyl, benzylcarbonyl, 9-fluorenylmethylcarbonyl, trifluoroacetyl, benzyl, triphenylmethyl, benzylidene, p-toluenesulfonyl, phthalimide, or succinimide. Protecting groups can be removed using standard techniques, see Greene's Protective Groups in Organic Synthesis [ protecting groups in the organic synthesis of Greene ], 4 th edition, wiley-Interscience.

Scheme 2

As shown in scheme 3, compounds of formula (III), wherein X ¹ and X ² are as defined for the compound of formula (III) in scheme 2, can be obtained by amide coupling conversion of the compound of formula (IV) and the amine compound of formula (V) by activating the carboxylic acid function of the compound of formula (IV), which is a process typically occurring by converting the-OH of the carboxylic acid to a good leaving group (such as a chloride group), for example by using (COCl) ₂ or SOCl ₂, followed by treatment with the compound of formula (IV), preferably in a suitable solvent (e.g. N-methylpyrrolidone, acetonitrile, dimethylacetamide, dichloromethane or tetrahydrofuran), preferably at a temperature between 25 ℃ and 60 ℃, and optionally in the presence of a base such as triethylamine or N, N-diisopropylethylamine.

Alternatively, compounds of formula (III) can be obtained using amidation coupling reagents such as 1-propanephosphonic acid cyclic anhydride (T3P) in a suitable solvent (e.g., acetonitrile), optionally in the presence of a base (e.g., triethylamine or N, N-diisopropylethylamine) under the conditions described in the literature for amide coupling. See, for example, chem.soc.rev. [ overview of the chemistry) 2009,38,606 and chem.soc.rev. [ overview of the chemistry ]2011,40,5084.

Scheme 3

As shown in scheme 4, the compound of formula (II) may be obtained by amide coupling conversion of the compound of formula (IV) and the amine compound of formula (VI) by activating the carboxylic acid function of the compound of formula (IV), which is a process that typically occurs by converting the-OH of the carboxylic acid to a good leaving group (such as a chloride group), for example by using (COCl) ₂ or SOCl ₂, followed by treatment with the compound of formula (IV), preferably in a suitable solvent (e.g. N-methylpyrrolidone, acetonitrile, dimethylacetamide, dichloromethane or tetrahydrofuran), preferably at a temperature between 25 ℃ and 60 ℃, and optionally in the presence of a base (such as triethylamine or N, N-diisopropylethylamine).

Alternatively, compounds of formula (II) can be obtained using amidation coupling reagents such as 1-propanephosphonic acid cyclic anhydride (T3P) in a suitable solvent (e.g., acetonitrile), optionally in the presence of a base (e.g., triethylamine or N, N-diisopropylethylamine) under the conditions described in the literature for amide coupling. See, for example, chem.soc.rev. [ overview of the chemistry) 2009,38,606 and chem.soc.rev. [ overview of the chemistry ]2011,40,5084.

Scheme 4

As shown in schemes 5a, 5B and 5C, respectively, the compounds of formula (I), (III) or (II) can also be prepared by reacting a nucleophilic compound of formula (VII) with an electrophilic compound of formula (VIII), (IX) or (X) (wherein X ¹ and X ² are as defined for the compound of formula (III) in scheme 2, and X ³ is a suitable leaving group such as fluorine, chlorine, bromine, iodine, ₃K、B(OH)₂ or B (pinacol)) in the presence of a base (e.g., KO-t-Bu, K ₃PO₄、K₂CO₃, triethylamine, or Cs ₂CO₃) in a suitable solvent (e.g., N-methylpyrrolidone, dimethylacetamide, acetonitrile, tetrahydrofuran, 2-methyltetrahydrofuran, sulfolane, or dimethylsulfoxide), at a temperature between 10 ℃ and 90 ℃ and preferably using a metal catalyst complex (e.g., cu or Pd). For related examples, see Eur.J. Org. Chem. [ J. European journal of organic chemistry ]2011,18,3353; J.Org. Chem. [ J. Organic chemistry ]2009,74,7951;Tetrahedron Lett. [ tetrahedral flash ],2012,53,5318. The compounds of formula (VII) are known or commercially available.

Scheme 5a

Scheme 5b

Scheme 5c

As shown in scheme 6, compounds of formula (VIII) can be obtained by intramolecular cyclization of a compound of formula (X) wherein X ³ is a suitable leaving group such as fluorine, chlorine, bromine, iodine, BF ₃K、B(OH)₂ or B (pinacol) in a suitable solvent or solvent mixture (e.g., dichloromethane, dimethylformamide, 2-methyltetrahydrofuran, tetrahydrofuran, diethyl ether, toluene, ethyl acetate) using a chlorinating agent (e.g., POCl ₃、PCl₅、(COCl)₂ or SOCl ₂), optionally in the presence of dimethylformamide, preferably at a temperature between 0 ℃ and 80 ℃, more preferably between 25 ℃ and 60 ℃. See, for example, chem.soc.rev. [ overview of the chemistry) 2009,38,606 and chem.soc.rev. [ overview of the chemistry ]2011,40,5084.

Scheme 6

As shown in scheme 7, compounds having formula (X) can be obtained by amine deprotection of a compound having formula (IX), wherein binding schemes 2, X ¹ and X ² are as defined for compounds having formula (III), and X ³ is a suitable leaving group such as fluorine, chlorine, bromine, iodine, BF ₃K、B(OH)₂ or B (pinacol). Protecting groups can be removed using standard techniques, see Greene's Protective Groups in Organic Synthesis [ protecting groups in the organic synthesis of Greene ], 4 th edition, wiley-Interscience.

Scheme 7

As shown in scheme 8, compounds of formula (IX), wherein the binding schemes 2, X ¹ and X ² are as defined for compounds of formula (III) and X ³ is a suitable leaving group, such as fluorine, chlorine, bromine, iodine, BF ₃K、B(OH)₂ or B (pinacol), can be prepared by the amide coupling conversion of a compound of formula (XI) and an amine compound of formula (V) by activating the carboxylic acid function of the compound of formula (XI), which is a process typically occurring by converting the-OH of the carboxylic acid to a good leaving group, such as a chloride group, for example by using (COCl) ₂ or SOCl ₂, followed by treatment with a compound of formula (V), preferably in a suitable solvent, such as N-methylpyrrolidone, dimethylacetamide, dichloromethane or tetrahydrofuran, preferably at a temperature between 25 ℃ and 60 ℃ and optionally in the presence of a base, such as triethylamine or N, N-diisopropylamine.

Alternatively, the compounds of formula (IX) can be obtained using amidation coupling reagents such as 1-propanephosphonic acid cyclic anhydride (T3P) in a suitable solvent (e.g., acetonitrile), optionally in the presence of a base (e.g., triethylamine or N, N-diisopropylethylamine) under the conditions described in the literature for amide coupling. See, for example, chem.Soc.Rev. [ review of chemistry ]2009,38,606 and chem.Soc.Rev. [ review of chemistry ]2011,40,5084.

The compounds of formula (V) are known, commercially available or readily available to the expert in the field.

Scheme 8

As shown in scheme 9, a compound of formula (X), wherein X ³ is a suitable leaving group such as fluorine, chlorine, bromine, iodine, BF ₃K、B(OH)₂ or B (pinacol), can also be obtained by subjecting the compound of formula (XI) and the amine compound of formula (VI) to an amide coupling conversion by activating the carboxylic acid function of the compound of formula (XI), which is a process typically occurring by converting the-OH of the carboxylic acid to a good leaving group such as a chloride group, for example by using (COCl) ₂ or SOCl ₂, followed by treatment with the compound of formula (VI), preferably in a suitable solvent such as N-methylpyrrolidone, dimethylacetamide, dichloromethane or tetrahydrofuran, preferably at a temperature between 25 ℃ and 60 ℃, and optionally in the presence of a base such as triethylamine or N, N-diisopropylethylamine;

Alternatively, the compounds of formula (X) can be obtained using amidation coupling reagents such as 1-propanephosphonic acid cyclic anhydride (T3P) in a suitable solvent (e.g., acetonitrile), optionally in the presence of a base (e.g., triethylamine or N, N-diisopropylethylamine) under the conditions described in the literature for amide coupling. See, for example, chem.Soc.Rev. [ review of chemistry ]2009,38,606 and chem.Soc.Rev. [ review of chemistry ]2011,40,5084.

The compounds of formula (VI) are known or commercially available.

Scheme 9

As shown in schemes 10a and 10B, respectively, compounds having formulas (I) and (III) can also be prepared by reacting a nucleophilic compound having formulas (XIII) and (XIV) with an electrophilic compound having formula (XII) (wherein binding schemes 2, X ¹ and X ² are as defined for compounds having formula (III) and X ³ is a suitable leaving group such as fluorine, chlorine, bromine, iodine, BF ₃K、B(OH)₂ or B (pinacol)) in the presence of a base (e.g., KO-t-Bu, K ₃PO₄、K₂CO₃, triethylamine, or Cs ₂CO₃) in a suitable solvent (e.g., N-methylpyrrolidone, dimethylacetamide, acetonitrile, tetrahydrofuran, 2-methyltetrahydrofuran, sulfolane, or dimethylsulfoxide), at a temperature between 10 ℃ and 90 ℃ and preferably using a metal catalyst complex (e.g., cu or Pd). For related examples, see Eur.J. Org. Chem. [ J. European journal of organic chemistry ]2011,18,3353; J.Org. Chem. [ J. Organic chemistry ]2009,74,7951;Tetrahedron Lett. [ tetrahedral flash ],2012,53,5318.

The compounds of formula (XII) are known or commercially available.

Scheme 10a

Scheme 10b

As shown in scheme 11, compounds having formula (XIII) can be obtained by intramolecular cyclization of compounds having formula (XV) in a suitable solvent or solvent mixture (e.g., dichloromethane, dimethylformamide, 2-methyltetrahydrofuran, tetrahydrofuran, diethyl ether, toluene, ethyl acetate) using a chlorinating agent, for example, by using poci ₃、PCl₅、(COCl)₂ or SOCl ₂, optionally in the presence of dimethylformamide, preferably at a temperature between 0 ℃ and 80 ℃, more preferably between 25 ℃ and 60 ℃. See, for example, chem.soc.rev. [ overview of the chemistry) 2009,38,606 and chem.soc.rev. [ overview of the chemistry ]2011,40,5084.

Scheme 11

As shown in scheme 12, compounds having formula (XV) can be obtained by amine deprotection of a compound having formula (XIV), wherein X ¹ and X ² are as defined for the compound having formula (III) in scheme 2. Protecting groups can be removed using standard techniques, see Greene's Protective Groups in Organic Synthesis [ protecting groups in the organic synthesis of Greene ], 4 th edition, wiley-Interscience.

Scheme 12

As shown in scheme 13, a compound having formula (XVII) (wherein X ⁴ is OH OR ¹) can be obtained by coupling a compound having formula (VI) with a compound having formula (XVI), wherein X ⁴ is as defined in the compound having formula (XVII) and X ⁵ is C ₁-C_4- alkoxy, such as methoxy OR ethoxy. Subsequent cyclization may be achieved using an acid, typically acetic acid, at a temperature between 20 ℃ and 120 ℃, more preferably between 80 ℃ and 120 ℃. See, for related examples, heterocycles [ Heterocycles ]2016,92,2166 and WO 2017/031325. The compounds of formula (VI) are known or may be readily available to an expert in the field.

Scheme 13

As shown in scheme 14, compounds having formula (XVI) (wherein X ⁴ is OH OR ¹ and X ⁵ is C ₁-C₄ -alkoxy, such as methoxy OR ethoxy) can be obtained by reacting compounds having formula (XVIII) at a temperature from-30 ℃ to 20 ℃ in the corresponding alcohol (e.g., sodium methoxide OR potassium tert-butoxide) OR an excess alcohol (such as methanol OR ethanol) and an alkali metal, typically in solution, using an alkoxide. Alternatively, the compound of formula (XVIII) can be hydrolyzed in the presence of an acid (e.g., hydrochloric acid) in a suitable solvent or solvent mixture (e.g., methanol, ethanol, dichloromethane, or 1, 4-dioxane) at a temperature from-30 ℃ to 40 ℃. For relevant examples, see WO 2012/178015, JP 2014/037370 or Angew.chem.int.ed. [ International edition of German application chemistry ]2020,59,23306.

Scheme 14

As shown in scheme 15, compounds having formula (XX), wherein X ⁶ is OH or C ₁-C₄ -alkoxy, such as methoxy or ethoxy, can also be prepared by reacting a compound having formula (XIX) in an aqueous solvent mixture, such as isopropanol or ethanol, optionally in a basic medium, at a temperature between 90 ℃ and 110 ℃. See J.Med. Chem. [ J.pharmaceutical chemistry ]2012,55,10118 for related examples.

Scheme 15

The compounds of formula (XIX) are known or, as shown in scheme 16, can be obtained by reacting a compound of formula (XXI), wherein X ⁷ is chloro, bromo, iodo, or O-trifluoromethanesulfonyl, with a metal source, such as XPhos Pd generation 1, in the presence of a cyanide source, such as potassium ferrocyanide, copper cyanide, zinc cyanide, or potassium cyanide, and a base, such as KOAc, in a suitable solvent or solvent mixture, such as dioxane, water, toluene, tetrahydrofuran, 2-methyl-tetrahydrofuran, xylene, at a temperature between 50 ℃ and 120 ℃, preferably between 80 ℃ and 110 ℃. For relevant examples, see J.org.chem. [ journal of organic chemistry ]2018,83,4922 and Org.let. [ organic flash ]2006,8,1189. The compounds of formula (XXI) are known or may be readily prepared by an expert in the field.

Scheme 16

As shown in scheme 17, compounds having formula (XVII) wherein X ⁴ is OH OR ¹ can also be obtained by cyclizing a compound having formula (XXII) using an acid (e.g., acetic acid, pure OR in a suitable solvent such as methanol OR ethanol) at a temperature from 20 ℃ to 75 ℃ followed by reduction in a solvent OR solvent mixture (such as tetrahydrofuran, toluene OR methanol) in the presence of a hydride (e.g., sodium cyanoborohydride, sodium borohydride, sodium triacetoxyborohydride OR lithium borohydride). For a related example, see WO 2016/201168.

Scheme 17

As shown in scheme 18, compounds having formula (XXII), wherein X ⁴ is OH OR ¹, can be obtained by reacting a compound having formula (XXIV), wherein X ⁸ is a leaving group such as chloro, bromo, iodo, methanesulfonyl, toluenesulfonyl OR O-trifluoromethanesulfonyl, with a compound having formula (XXIII), optionally in the presence of a base such as pyridine, triethylamine, potassium carbonate, sodium carbonate, in a suitable solvent OR solvent mixture such as benzene, toluene, tetrahydrofuran, chloroform, acetonitrile OR 2-methyl-tetrahydrofuran, at a temperature between 0 ℃ and 110 ℃, more preferably between 20 ℃ and 80 ℃. For relevant examples, see J.Med. Chem. [ J.pharmaceutical chemistry ]2011,54,8407;WO 2002/051811 or WO 2010/078867. The compounds of formula (XXIV) are known or readily available to an expert in the field.

Scheme 18

Compounds having formula (XXIII), wherein X ⁴ is OH OR ¹, are known OR can be prepared as shown in scheme 19 by reacting a compound having formula (XVIII) using hydroxylamine OR a hydroxylamine salt (such as hydrochloride), optionally in the presence of a base (e.g., potassium carbonate OR sodium carbonate), in a suitable solvent OR solvent mixture (e.g., methanol, ethanol, 2-methyl-2-butanol, water, OR 1-butyl-3-methylimidazole acetate). For relevant examples, see Org.Biomol.chem. [ organic and biomolecular chemistry ]2014,12,8036;WO 2016/143655 or WO 201/9224743. The compounds of formula (XVIII) are known, commercially available or readily available to the expert in the field.

Scheme 19

As shown in scheme 20, a compound having formula (XXVI) or a lithium, sodium or barium salt thereof, wherein X ⁵ is C ₁-C₄ -alkoxy, e.g., methoxy or ethoxy, can be prepared by reacting a nucleophilic compound having formula (VII) with an electrophilic compound having formula (XXV) wherein X ⁵ is C ₁-C₄ -alkoxy, e.g., methoxy or ethoxy, and X ³ is a suitable leaving group, e.g., fluorine, chlorine, bromine, iodine, BF ₃K、B(OH)₂ or B (pinacol), in a suitable solvent or solvent mixture, e.g., N-methylpyrrolidone, dimethylacetamide, acetonitrile, tetrahydrofuran, 2-methyltetrahydrofuran, sulfolane, dimethylsulfoxide, at a temperature between 20 ℃ and 110 ℃ and preferably using a metal catalyst complex, e.g., cu or Pd, in the presence of a base, e.g., KO-t-Bu, K ₃PO₄、K₂CO₃, triethylamine, or Cs ₂CO₃. For related examples, see Eur.J.Org.chem. [ European journal of organic chemistry ]2011,18,3353; J.Org.chem. [ journal of organic chemistry ]2009,74,7951;Tetrahedron Lett. [ tetrahedral flash ]2012,53,5318;WO 2008/110313 and WO 2012/136604. The compounds of formula (VII) are known or commercially available.

The compound of formula (IV) can then be obtained by hydrolyzing a compound of formula (XXVI) (wherein X ⁵ is C ₁-C₄ -alkoxy, such as methoxy or ethoxy) with an alkaline hydroxide (such as lithium hydroxide, sodium hydroxide, potassium hydroxide or barium hydroxide) in a suitable solvent or solvent mixture (e.g. methanol, acetonitrile, ethanol, water, tetrahydrofuran or 2-methyl-tetrahydrofuran) at a temperature between 0 ℃ and 80 ℃. Alternatively, the esters may be cleaved under acidic conditions using, for example, hydrochloric acid. For relevant examples, see WO 2021/086879 or org.Biomol.chem. [ organic and biomolecular chemistry ]2015,13,7928.

Scheme 20

As shown in scheme 21, compounds having formula (XX), wherein X ⁶ is OH or C ₁-C₄ -alkoxy, such as methoxy or ethoxy, can also be prepared by reacting a nucleophilic compound having formula (XXVII), wherein X ⁶ is as defined for a compound having formula (XX), with an electrophilic compound having formula (XII), wherein X ³ is a suitable leaving group, such as fluorine, chlorine, bromine, iodine, BF ₃K、B(OH)₂ or B (pinacol), in a suitable solvent, such as dichloromethane, 1, 2-dichloromethane, acetonitrile, tetrahydrofuran, 2-methyltetrahydrofuran, N-methylpyrrolidone, dimethylacetamide, dimethyl ether, or toluene, at a temperature between 20 ℃ and 80 ℃ and using a metal source, such as Cu (OAc) ₂, preferably in the presence of an oxidizing agent such as O ₂ or a suitable palladium pre-catalyst, such as RockPhos Pd generations, in the presence of a base, such as K ₃PO₄. For related examples, see org.lett. [ organic flash ]2003,5,1381;Tetrahedron Lett @ [ tetrahedral flash ]1998,39,2933;Tetrahedron Lett @ [ tetrahedral flash ]2003,44,3863 and org.lett. [ organic flash ]2013,15,2876.

The compounds of formula (XII) are known or commercially available.

Scheme 21

As shown in scheme 22, a compound having formula (XXX) or a lithium, sodium or barium salt thereof, wherein X ⁹ is OH or halogen, may be obtained from a compound having formula (XXIX) by hydrolysis in a manner similar to that described for the conversion of a compound having formula (XXVI) to a compound having formula (IV) in scheme 20.

Compounds having formula (XXIX), wherein X ⁵ is C ₁-C₄ -alkoxy, such as methoxy or ethoxy, and X ⁹ is OH or halogen, can be obtained from compounds having formula (XXVIII), wherein X ⁹ is OH or halogen, via an oxidation process using a suitable oxidizing agent, such as KMnO ₄ or cobalt (ll) salts, and trihydroxy isocyanuric acid (THICA), in a suitable solvent, such as acetic acid, at a temperature between 25 ℃ and 200 ℃. For relevant examples, see can.J.chem. [ J.Canadian chem., 1978,56,1273 and WO 2021/160470. The compounds of formula (XXVIII) are known or can be prepared as described in Bulletin de la Societe Chimique de France [ French chemical Association ]1972,8,3198.

Scheme 22

As shown in scheme 23, compounds having formula (XXXIII), wherein X ⁵ is C ₁-C₄ -alkoxy, such as methoxy or ethoxy, can be obtained from compounds having formula (XXXIII) via an oxidation process using a suitable oxidizing agent, such as KMnO ₄ or a suitable cobalt (ll) salt and trihydroxy isocyanuric acid (THICA), in a suitable solvent, such as acetic acid, at a temperature between 25 ℃ and 200 ℃. For relevant examples, see can.J.chem. [ J.Canadian chem., 1978,56,1273 and WO 2021/160470.

Furthermore, compounds having formula (XXXII) may be prepared by reacting a nucleophilic compound having formula (VII) with an electrophilic compound having formula (XXXI) wherein X ³ is a suitable leaving group such as fluorine, chlorine, bromine, iodine, BF ₃K、B(OH)₂ or B (pinacol) in the presence of a base (e.g., KO-t-Bu, K ₃PO₄、K₂CO₃, triethylamine, or Cs ₂CO₃) in a suitable solvent (e.g., N-methylpyrrolidone, dimethylacetamide, acetonitrile, tetrahydrofuran, 2-methyltetrahydrofuran, sulfolane, dimethylsulfoxide), at a temperature between 25 ℃ and 120 ℃, and refluxing, and optionally using a metal catalyst and a ligand complex (e.g., cuI, N-dimethylglycine). For related examples, see Eur.J.Org.chem. [ European journal of organic chemistry ]2011,18,3353; J.Org.chem. [ journal of organic chemistry ]2009,74,7951;Tetrahedron Lett. [ tetrahedral flash ]2012,53,5318;WO 2008/110313 and WO 2012/136604. The compounds of formula (XXXI) are known or commercially available.

Scheme 23

As shown in scheme 24, compounds of formula (XX), wherein X ⁶ is OH or C ₁-C₄ -alkoxy, such as methoxy or ethoxy, can also be obtained from compounds of formula (XXI), wherein X ⁷ is chloro, bromo, iodo, or trifluoromethanesulfonyl-O-) using a metal source, such as XPhos Pd G1, at a temperature between 20 ℃ and 130 ℃, preferably between 70 ℃ and 110 ℃, in a pressure vessel, typically a stainless steel autoclave, loaded with carbon monoxide, under a pressure typically between 1 and 50 bar, more preferably between 5 and 15 bar, in the presence of an organic base, such as triethylamine or diisopropylethylamine, and a suitable solvent, such as methanol or ethanol. See J.Med. Chem. [ J. Pharmaceutical chemistry ]2014,57,2692 and adv. Synth. Catalyst. [ higher synthesis catalysis ]2006,348,1255 for related examples.

Scheme 24

Alternatively, as shown in scheme 25, the compound having formula (IV) may also be obtained by reacting a compound having formula (XXXIV), wherein X ¹⁰ is chloro, bromo or iodo, with a lithium reagent (e.g., n-butyllithium, sec-butyllithium, tert-butyllithium or diisopropylamine lithium) in a suitable solvent (e.g., hexane, diethyl ether or tetrahydrofuran) at a temperature between-78 ℃ and-30 ℃ followed by the addition of carbon dioxide. See J.Am.chem.Soc. [ journal of American society of chemistry ]2018,140,9140 and J.Am.chem.Soc. [ journal of American society of chemistry ]2021,143,1539 for related examples.

Scheme 25

Compounds having formula (XXXIV) wherein X ¹⁰ is chloro, bromo or iodo are known or can be prepared as shown in scheme 26 by reacting a compound having formula (XXXV) with an electrophilic halogen reagent like bromo, dibromohydantoin, N-bromo-or N-chloro-succinimide in a suitable solvent, e.g. chloroform, 2-methyltetrahydrofuran or dimethylformamide, optionally with a base, typically lithium diisopropylamine or N-butyllithium, at a temperature between-78 ℃ and 10 ℃. The compounds of formula (XXXV) are known, commercially available or readily prepared by an expert in the field. For relevant examples, see Tetrahedron Lett [ Tetrahedron flash ]2003,44,823; J.Am.chem.Soc. [ journal of the American society of chemistry ]2010,132,8858 and Synthesis [ Synthesis ]2005,16,2782.

Scheme 26

As shown in scheme 27, compounds having formula (IV) can also be prepared by reacting a compound having formula (XXXV) with a base (typically lithium diisopropylamine or n-butyllithium) at a temperature between-78 ℃ and 10 ℃, optionally in the presence of a catalyst (e.g., potassium tert-butoxide), in a suitable solvent (e.g., diethyl ether, cyclopentyl methyl ether, methyl tert-butyl ether, or tetrahydrofuran), followed by the addition of carbon dioxide. The compounds of formula (XXXV) are known, commercially available or readily prepared by an expert in the field. For relevant examples, see bioorg.Med.chem. [ bioorganic and pharmaceutical chemistry rapid report ]2004,12,5579, J.Am.chem.Soc. [ journal of American society of chemistry ]2010,132,8858 and Synthesis [ Synthesis ]2005,16,2782.

Scheme 27

As shown in scheme 28, compounds having formula (XXXIV) wherein X ¹⁰ is chloro, bromo or iodo are known or can be obtained from tautomers having formulas (XXXVI) and (XXXVII) by treatment with a phosphorus compound (e.g., phosphorus oxychloride, phosphorus pentachloride or phosphorus tribromide) in a suitable solvent (e.g., toluene, acetonitrile, dichloromethane or chloroform), optionally in the presence of a sub-stoichiometric amount of a catalyst (e.g., triphenylphosphine or 4- (dimethylamino) pyridine). For relevant examples, see Tetrahedron letters 2012,53,674, synth.Commun, synthetic communication 2016,46,1619 and J.org.chem, journal of organic chemistry 2011,76,4149. All such tautomers of formulae (XXXVI) and (XXXVII) and mixtures thereof in all proportions are contemplated herein.

Scheme 29

As shown in scheme 30, tautomers of formulas (XXXVII) and (XXXVII) are known or can be prepared by one pot nucleophilic addition, preferably in a suitable solvent (e.g., ethanol, isopropanol, dimethylformamide, acetic acid or acetonitrile), at a temperature between 50 ℃ and 110 ℃, optionally in the presence of a base (e.g., potassium carbonate, triethylamine), followed by cyclization using a compound of formula (XXXVIII) (wherein X ¹¹ is C ₁-C₄ alkyl or C ₅-C₆ cycloalkyl, or forms a saturated heterocycle with the nitrogen to which they are attached, and X ⁶ is OH or C ₁-C₄ -alkoxy, such as methoxy or ethoxy) and a compound of formula (XXXIX) or a hydrochloride thereof (wherein Q ⁷、Q⁸ and Q ⁹ are as defined for a compound of formula (I) and X ¹³ is H or a protecting group (e.g., tetrahydrofuran, 2- (trimethylsilyl) ethoxybenzyl or benzyl)). For relevant examples, see U.S. Pat. No. 5,311,0157, synthesis [ Synthesis ]2006,1,59 and WO 2010/016005. The compound having the formula (XXXIX) or a salt thereof is known or commercially available. All such tautomers of formulae (XXXV) and (XXXVI) and mixtures thereof in all proportions are contemplated herein.

Scheme 30

Compounds having formulae (XXXVI) and (XXXVII) are shown below, wherein Q ^a、Q^b、Q⁷、Q⁸、Q⁹ and R ¹ are as defined for compounds having formula (I):

As shown in scheme 31, compounds having formulas (XXXVI) and (XXXVII) may be prepared by intramolecular cyclization of a compound having formula (XL) or its hydrochloride salt (wherein Q ⁷、Q⁸ and Q ⁹ are as defined for a compound having formula (I) and X ¹¹ is C ₁-C₄ alkyl or C ₅-C₆ cycloalkyl or forms a saturated heterocycle together with the nitrogen to which they are attached) in a suitable solvent (e.g., water or ethanol) at a temperature between 20 ℃ and 100 ℃. For a related example, see WO 2005/012662. All such tautomers of formulae (XXXV) and (XXXVI) and mixtures thereof in all proportions are contemplated herein.

Scheme 31

As shown in scheme 32, tautomers having the corresponding formulae (XXXVI) and (XXXVII) can be prepared by amination and direct cyclization in a suitable solvent (e.g., dimethyl sulfoxide, dimethylformamide, dichloromethane, N-methyl-2-pyrrolidone, or ethanol), at a temperature between 0 ℃ and 110 ℃, more preferably between 20 ℃ and 50 ℃, optionally in the presence of a base (e.g., KOH, naOH), from a compound having formula (XLI) (wherein Q ⁷、Q⁸ and Q ⁹ are as defined for a compound having formula (I), X ¹¹ is C ₁-C₄ alkyl or C ₅-C₆ cycloalkyl or forms a saturated heterocycle together with the nitrogen to which they are attached, and X ¹³ is H or a protecting group (e.g., tetrahydrofuran, 2- (trimethylsilyl) ethoxymethyl, or benzyl)), i.e., by reaction with an amination reagent (e.g., amino 4-nitrobenzoate, N- (tert-butoxycarbonyl) -2-nitrobenzenesulfonamide, hydroxylamine-O-sulfonic acid, or sodium diformylamide). For relevant examples, see J.Med. Chem. J. Eur. Chem. 1996,39,582; organometallics [ organometallic ]2014,33,4035 and chem. Eur. J. European J. 2019,25,1963. All such tautomers of formulae (XXXV) and (XXXVI) and mixtures thereof in all proportions are contemplated herein.

Scheme 32

As shown in scheme 33, a compound of formula (XL) or a hydrochloride salt thereof, wherein Q ⁷、Q⁸ and Q ⁹ are as defined for a compound of formula (I) and X ¹¹ is C ₁-C₄ alkyl or C ₅-C₆ cycloalkyl or forms a saturated heterocycle together with the nitrogen to which they are attached, can be obtained by aminating a compound of formula (XLIII) wherein Q ⁷、Q⁸ and Q ⁹ are as defined for a compound of formula (I) and X ¹¹ is as defined for a compound of formula (XL) in a suitable solvent, e.g., dimethyl sulfoxide, N-methyl-2-pyrrolidone or dimethylacetamide, at a temperature between 20 ℃ and 120 ℃. For relevant examples, see Dalton Trans [ Dalton J.Ind. ]2016,45,15644, J.Med. Chem. [ J.pharmaceutical chemistry J. ]1996,39,582 or chem. Eur. J. [ J.European chemistry J. ]2019,25,1963.

Scheme 33

As shown in scheme 34, compounds of formula (XLI) wherein Q ⁷、Q⁸ and Q ⁹ are as defined for compounds of formula (I) and X ¹¹ is C ₁-C₄ alkyl or C ₅-C₆ cycloalkyl or forms a saturated heterocycle together with the nitrogen to which they are attached and X ¹³ is H or a protecting group (e.g., tetrahydrofuran, 2- (trimethylsilyl) ethoxymethyl or benzyl)) can be obtained from compounds of formula (XLIII) wherein Q ⁷、Q⁸ and Q ⁹ are as defined for compounds of formula (I) and X ¹³ is as defined for compounds of formula (XLI) by reaction with pure formamide synthetic equivalents (e.g., dimethylformamide dimethyl acetal or 1- (dimethoxymethyl) pyrrolidine) or in a suitable solvent (e.g., toluene, dimethylformamide) at a temperature between 50 ℃ and 120 ℃. For relevant examples, see WO 2021/2296621, WO 2008/149379 and Bioorg. Med. Chem. Lett. [ bioorganic and pharmaceutical chemistry rapid report ]2022,61,128552.

Scheme 34

As shown in scheme 35, compounds of formula (XLIII) (Q ⁷、Q⁸ and Q ⁹ are as defined for compounds of formula (I) and X ¹³ is H or a protecting group (e.g., tetrahydrofuran, 2- (trimethylsilyl) ethoxymethyl or benzyl)) can be prepared using an organometallic reagent (e.g., methyl magnesium bromide, isopropyl magnesium chloride, lithium chloride, butyllithium, tert-butyllithium or phenyl magnesium chloride) in a suitable solvent (e.g., tetrahydrofuran, diethyl ether, cyclopentyl methyl ether or 2-methyltetrahydrofuran) at a temperature between-78 ℃ and 15 ℃, more preferably between-20 ℃ and 10 ℃ from compounds of formula (XLIV) and compounds of formula (Q ⁷、Q⁸ and Q ⁹ are as defined for compounds of formula (I) wherein X ¹⁰ is chloro, bromo or iodo and X ¹³ is as defined for compounds of formula (XLIII). For relevant examples, see WO 2009/130193 and WO 2015/057205.

Scheme 35

The compounds of formula (XLIV) are known or, as shown in scheme 36, can be obtained by reacting a compound of formula (XLVI) or a lithium, sodium or barium salt thereof with N, O-dimethylhydroxylamine hydrochloride in a suitable solvent or solvent mixture (e.g., dimethylformamide, dichloromethane, tetrahydrofuran, 2-methyltetrahydrofuran) at a temperature between-10 ℃ and 80 ℃, more preferably between 0 ℃ and 30 ℃, or in a suitable solvent or solvent mixture (e.g., dimethylformamide, dichloromethane, trichloromethane, tetrahydrofuran, 2-methyltetrahydrofuran) at a temperature between 0 ℃ and 80 ℃, optionally in the presence of a coupling agent (e.g., T3P, HATU, COMU). For relevant examples, see WO 2011/023706 and J.Med.chem. [ J.pharmaceutical chemistry ]2004,47,2405. The compounds of formula (XLVI) are known, commercially available or readily prepared by an expert in the field.

Scheme 36

As shown in scheme 37, compounds having formula (XLVIII), wherein X ⁵ is OH or C ₁-C₄ -alkoxy, X ¹¹ is C ₁-C₄ alkyl or C ₅-C₆ cycloalkyl or forms a saturated heterocycle together with the nitrogen to which they are attached, can be prepared by reacting pure compounds having formula (XLVIII), wherein X ⁵ is as defined for compounds having formula (XLVIII), in the presence of C ₁-C₆ -alkoxy-or C ₁-C₆ -cycloalkoxy-N, N '-tetra (C ₁-C₆ -alkyl or C ₁-C₆ -cycloalkyl) ethylenediamine (e.g., methoxy-or t-butoxy-N, N' -tetramethylethylenediamine) or in a suitable solvent or solvent mixture (e.g., dimethylformamide, 2-methyltetrahydrofuran) at a temperature between 25 ℃ and 120 ℃. For relevant examples, see Tetrahedron [ Tetrahedron report ]1998,54,9799; J.Het.chem. [ J. Heterocyclic chemistry ]2014,51,954 and Synth. Commun. [ synthetic communication ]2021,51,2160). The compounds of formula (xlviii) are known, commercially available or readily prepared by an expert in the art, for example from the compound of formula (XLV) of scheme 36.

Scheme 37

As shown in scheme 38, tautomers having formulas (XXXVI) and (XXXVII) can be prepared by reacting a nucleophilic tautomer compound having formulas (XLIX) and (L) with an electrophilic compound having formula (XII), wherein X ³ is a suitable leaving group such as fluorine, chlorine, bromine, iodine, BF ₃K、B(OH)₂ or B (pinacol), in the presence of a base such as K ₃PO₄ and a suitable solvent such as 1, 2-dimethoxyethane or toluene, in a suitable solvent such as dichloromethane, 1, 2-dichloromethane, acetonitrile, tetrahydrofuran, 2-methyltetrahydrofuran, N-methylpyrrolidone, dimethylacetamide at a temperature between 40 ℃ and 80 ℃ and using a catalyst such as Cu (OAc) ₂, and preferably in the presence of an oxidizing agent such as O ₂, alternatively using a suitable palladium pre-catalyst such as RockPhos Pd G3, at a temperature between 20 ℃ and 80 ℃. For related examples, see org.lett. [ organic flash ]2003,5,1381;Tetrahedron Lett @ [ tetrahedral flash ]1998,39,2933;Tetrahedron Lett @ [ tetrahedral flash ]2003,44,3863 and org.lett. [ organic flash ]2013,15,2876. The compounds of formula (XII) are known or commercially available. All such tautomers of the formulae (XXXV), (XXXVI), (XLIX) and (L) and mixtures thereof in all proportions are contemplated herein.

Scheme 38

Alternatively, as shown in scheme 39, compounds having the corresponding formulas (XXXVI) and (XXXVII) can be prepared from tautomers having formulas (LI) and (LII) (wherein X ¹⁰ is chloro, bromo or iodo) by reacting with a compound having formula (VII) (wherein X ³ is a suitable leaving group such as fluoro, chloro, bromo, iodo, BF ₃K、B(OH)₂ or B (pinacol)) at a temperature between 50 ℃ and 110 ℃ and preferably using a metal catalyst complex (e.g., cu or Pd) optionally in the presence of a base (e.g., KO-t-Bu, K ₃PO₄、K₂CO₃, triethylamine, or Cs ₂CO₃) in a suitable solvent or solvent mixture (e.g., N-methylpyrrolidone, dimethylacetamide, acetonitrile, tetrahydrofuran, 2-methyltetrahydrofuran, sulfolane, dimethylsulfoxide). For related examples, see Eur.J.Org.chem. [ European journal of organic chemistry ]2011,18,3353; J.Org.chem. [ journal of organic chemistry ]2009,74,7951;Tetrahedron Lett. [ tetrahedral flash ]2012,53,5318;WO 2008/110313 and WO 2012/136604. The compounds of formula (VII) are known or commercially available. All such tautomers of the formulae (XXXV), (XXXVI), (LI) and (LII) and mixtures thereof in all proportions are contemplated herein.

Scheme 39

As shown in scheme 40, tautomers having formulas (LI) and (LII), wherein X ¹⁰ is chloro, bromo, or iodo, can be obtained from tautomers having formulas (LIII) and (LIV) by treatment with hydrochloric acid or hydrogen bromide, optionally in the presence of a transition metal (e.g., zinc, palladium), or by treatment with sodium nitrate at a temperature between 0 ℃ and 50 ℃ in a suitable solvent or solvent mixture (e.g., water, acetonitrile, ethanol), followed by the addition of a copper salt (e.g., bromide or chloride). See MENDELEEV COMMUN for related examples [ Mendeleev communications ]2017,27,285.

Scheme 40

As shown in scheme 41, tautomers of formulas (LIII) and (LIV) can be obtained from a compound of formula (XXXIX) or its hydrochloride salt (wherein Q ⁷、Q⁸ and Q ⁹ are as defined for a compound of formula (I) and X ¹³ is H or a protecting group (e.g. tetrahydrofuran, 2- (trimethylsilyl) ethoxymethyl or benzyl)) by treatment with sodium or potassium nitrite, sodium hypochlorite or sodium azide in the presence of a strong acid (e.g. hydrochloric acid, trifluoroacetic acid, sulfuric acid, nitric acid) in a suitable solvent (typically water or acetonitrile) at a temperature between-10 ℃ and 30 ℃ to obtain the diazonium salt. For relevant examples, see J.org.chem. [ journal of organic chemistry ]2010,75,8487; bioorg.Med. Chem. Lett. [ journal of bioorganic and pharmaceutical chemistry ]2020,30,127216 and J.org.chem. [ journal of organic chemistry ]1987,52,5538. The resulting diazonium salt may be reacted with a nitro compound (e.g., 4- (2-nitrovinyl) morpholine, 2-nitroacetaldehyde, 2-nitromalonaldehyde, 2-nitromalonate 1, 3-diethyl ester) in a suitable solvent or solvent mixture (e.g., water or ethanol), at a temperature between 0 ℃ and 60 ℃, optionally in the presence of a base (e.g., na ₂CO₃、K₂CO₃, KOH) or a strong acid (e.g., nitric acid, hydrochloric acid). See MENDELEEV COMMUN for related examples [ Mendeleev communications ]2017,27,285;WO 2017/144708 or Khimiya Geterotsiklicheskikh Soedinenii [ heterocyclic chemical ]1986,5,662. The compound of formula (XXXIX) or a hydrochloride thereof is known, commercially available or readily available to an expert in the field.

Scheme 41

As shown in scheme 42, a compound having formula (XX) (wherein X ⁶ is OH or C ₁-C₄ -alkoxy, such as methoxy or ethoxy) can be obtained by reacting a compound having formula (LVI) or a hydrochloride thereof (wherein X ⁶ is as defined for the compound having formula (XX)) with a compound having formula (LVII) (wherein X ¹⁴ and X ¹⁵ are the same or different, independently selected from chloro, bromo, iodo, O-methanesulfonyl, O-toluenesulfonyl, O-trifluoromethanesulfonyl or carbonyl or oxo equivalent, such as aldehyde, acetal, acyl chloride or bromide, ester or orthoester), at a temperature between 30 ℃ and 125 ℃, optionally in a microwave reactor, in the presence of a catalyst (e.g., hydrogen bromide or sodium carbonate), optionally in a suitable solvent or solvent mixture (e.g., dimethylformamide, dimethyl sulfoxide, toluene, ethanol, isopropanol, water). For relevant examples, see J.Med. Chem. [ J.pharmaceutical chemistry ]2021,64,1197;Tetrahedron Lett [ tetrahedron flash ]2017,58,4816 and chem.Pharm. Bull. [ chemical and pharmaceutical Instructions ]1992,40,1170. Compounds having the formula (LVII) are known or commercially available.

Scheme 42

As shown in scheme 43, a compound having formula (LVI) or a hydrochloride thereof, wherein R ¹ is as defined for a compound having formula (I) and X ⁶ is OH or C ₁-C₄ -alkoxy, such as methoxy or ethoxy, can be obtained by nucleophilic displacement of a compound having formula (LVIII) wherein R ¹ and X ⁶ are as defined for a compound having formula (LVI) and X ¹⁶ is an alkyl or cycloalkyl group, such as methyl, ethyl or cyclohexyl, over a sulfone in the presence of an amination reagent (e.g., NH ₄OH、NH₃、NH₄ OAc) and optionally in the presence of a base (e.g., triethylamine) in a suitable solvent or solvent mixture (e.g., dimethyl sulfoxide, water, tetrahydrofuran, 1, 4-dioxane, isopropanol, ethanol, methanol, dichloromethane). For relevant examples, see Tetrahedron [ Tetrahedron report ]2009,65,1697, heterocycles [ 1977,8,299 and org.biomol.chem. [ organic biomolecular chemistry ]2015,13,10620.

Scheme 43

As shown in scheme 44, compounds having formula (LVIII) wherein R ¹ is as defined for compounds having formula (I), X ⁶ is OH or C ₁-C₄ -alkoxy, such as methoxy or ethoxy, and X ¹⁶ is an alkyl or cycloalkyl group, such as methyl, ethyl or cyclohexyl, can be obtained by oxidizing a compound having formula (LIX) wherein R ¹、X⁶ and X ¹⁶ are as defined for compounds having formula (LVIII) in the presence of an oxidizing agent, such as 3-chloroperoxybenzoic acid, hydrogen peroxide, potassium hydrogen persulfate (oxone), chlorine, in a suitable solvent or solvent mixture, such as dichloromethane, acetonitrile, chloroform, water, toluene or 2-methyl-tetrahydrofuran, at a temperature between-10 ℃ and 50 ℃. For relevant examples, see chem.Eur.J. [ J.European chem ]2021,27,14826; J.Org.chem. [ J.Organic chem ]2017,82,2664 and J.chem.Soc. (C) Organic [ J.chem. (C): organic ]1967,7,568.

Scheme 44

As shown in scheme 45, a compound of formula (LIX) wherein R ¹ is as defined for a compound of formula (I), X ⁶ is OH or C ₁-C₄ -alkoxy, e.g. methoxy or ethoxy, and X ¹⁶ is an alkyl or cycloalkyl group, e.g. methyl, ethyl or cyclohexyl, can be obtained by reacting a compound of formula (LX) wherein X ⁶ and X ¹⁶ are as defined for a compound of formula (LVIII), and X ³ is a suitable leaving group, e.g. fluoro, chloro, bromo, iodo, BF, ₃K、B(OH)₂ B or pinacol, in a suitable solvent, e.g. N-methylpyrrolidone, dimethylacetamide, acetonitrile, tetrahydrofuran, 2-methyltetrahydrofuran, sulfolane, dimethylsulfoxide, at a temperature between 25 ℃ and 110 ℃ and under reflux, and optionally using a metal catalyst and a ligand complex, e.g. CuI, lvn, N-dimethylglycine, in the presence of a base, e.g. KO-t-Bu, K ₃PO₄、K₂CO₃, triethylamine, or Cs ₂CO₃. For related examples, see Eur.J.Org.chem. [ European journal of organic chemistry ]2011,18,3353; J.Org.chem. [ journal of organic chemistry ]2009,74,7951;Tetrahedron Lett. [ tetrahedral flash ]2012,53,5318;WO 2008/110313 and WO 2012/136604. The compounds of formula (LX) are known or readily available to an expert in the field.

Scheme 45

As shown in scheme 46, the compounds having formula (V) can be prepared by mixing, optionally in a suitable solvent or solvent mixture (e.g., dichloromethane, tetrahydrofuran, 2-methyltetrahydrofuran or diethyl ether) at a temperature between 0 ℃ and 50 ℃ with an acid (e.g., hydrochloric acid, Trifluoroacetic acid) treating a compound having the formula (LXI) (wherein X ¹ is H and X ² is a protecting group, or X ¹ and X ² are the same or different protecting groups, or X ¹ and X ² together with the nitrogen to which they are attached form a protecting group, and wherein X ^1a is H and X ^2a is a protecting group, or X ^1a and X ^2a are the same or different protecting groups, or X ^1a and X ^2a together with the nitrogen to which they are attached form a protecting group, and X ² is different from X ^2a. x ¹ and X ^1a may both be hydrogen. In addition, if on the one hand X ¹ and X ² and on the other hand X ^1a and X ^2a form a protecting group together with the nitrogen to which they are attached, the protecting groups should be different. Examples of protecting groups include, for example, t-butyloxycarbonyl, benzylcarbonyl, 9-fluorenylmethylcarbonyl, trifluoroacetyl, benzyl, triphenylmethyl, benzylidene, p-toluenesulfonyl, phthalimide, or succinimide.

Wherein the protecting groups X ¹ and X ² are the same or different, optionally together with the nitrogen to which they are attached form a ring, such as t-butyloxycarbonyl, benzylcarbonyl, 9-fluorenylmethylcarbonyl, trifluoroacetyl, benzyl, phthaloyl, triphenylmethyl, benzylidene or p-toluenesulfonyl). See ChemBioChem [ biochemistry ]2009,10,323 and org.process res.dev ] [ organic engineering research and development ]2002,6,520 for related examples.

Compounds of formula (LXI) are known or readily available to an expert in the art.

Scheme 46

As indicated, surprisingly, it has now been found that for practical purposes the compounds of formula (I) according to the invention have a very advantageous level of biological activity for protecting plants against diseases caused by fungi.

The compounds of formula (I) can be used in the agricultural sector and related fields of use, for example as active ingredients for controlling plant pests, or on non-living materials for controlling spoilage microorganisms or organisms potentially harmful to humans. These novel compounds are distinguished by excellent activity at low application rates, good plant tolerance and environmental safety. They have very useful therapeutic, prophylactic and systemic properties and can be used to protect many cultivated plants. The compounds of formula (I) can be used to inhibit or destroy pests that occur on plants or plant parts (fruits, flowers, leaves, stems, tubers, roots) of different crops of useful plants, while also protecting those plant parts that grow later from, for example, phytopathogenic microorganisms.

The invention further relates to a method for controlling or preventing infestation of plants or plant propagation material and/or harvested food crops which are susceptible to attack by microorganisms by treating the plants or plant propagation material and/or harvested food crops, wherein an effective amount of a compound of formula (I) is applied to these plants, parts thereof or the locus thereof.

Compounds having formula (I) can also be used as fungicides. As used herein, the term "fungicide" means a compound that controls, alters, or prevents the growth of fungi. The term "fungicidally effective amount" when used means the amount of such compound or combination of such compounds that is capable of affecting fungal growth. Controlling or altering effects includes all deviations from natural development, such as killing, retardation, etc., and preventing barriers or other defensive structures included in or on plants to prevent fungal infection.

The compounds of formula (I) can also be used as seed dressing agents for the treatment of plant propagation material (e.g. seeds, such as fruits, tubers or grains) or plant cuttings, for protection against fungal infections as well as against phytopathogenic fungi present in the soil. The propagation material may be treated with a composition comprising a compound of formula (I) prior to planting, for example seed dressing may be performed prior to sowing. The active compounds having formula (I) can also be applied to the cereal grains (coating) by dipping the seeds in a liquid formulation or by coating them with a solid formulation. The composition may also be applied to the planting site at the time of planting the propagation material, such as to the furrow of the seed during sowing. The invention also relates to such a method of treating plant propagation material, and to plant propagation material so treated.

Furthermore, the compounds of formula (I) can be used in the relevant field for controlling fungi, for example for industrial material (including wood and industrial products related to wood) protection, food storage, hygiene management.

In addition, the present invention can be used to protect non-living materials (e.g., wood, wallboard, and paint) from fungal attack.

Compounds having formula (I) are useful, for example, against disease fungi and fungal vectors, and phytopathogenic bacteria and viruses. Fungi and fungal vectors of these diseases and phytopathogenic bacteria and viruses are for example:

cephalosporium parapsilosis, alternaria species, rhapontici species, cephalosporium species, aspergillus species (including Aspergillus flavus, aspergillus fumigatus, aspergillus nidulans, aspergillus niger, aspergillus terreus), aureobasidium species (including Aureobasidium pullulans), alternaria dermatitis, alternaria wheat powdery mildew, bremia lactucae (Bremia lactucae), phyllostachys species (including Botrytis cinerea (B. Dothidea), phyllostachys striolata (B. Obtusa)), vitis species (including Botrytis cinerea (B. Cinerea)), candida species (including Candida albicans), Candida glabrata (c.glabra), candida krusei (c.krusei), candida crescens (c.lusitaniae), candida parapsilosis (c.parapsilosis), candida tropicalis (c.tropicalis)), cephaloascus fragrans, coralloides species, cercospora species (including brown spot bacteria (c.arachidiola)), late spot bacteria (Cercosporidium personatum), cladosporium species, ergot bacteria, The species may be selected from the group consisting of Coccosporium crudus, proteus species, anthrax species (including banana anthracis (C. Musae)), cryptococcus neoformans, oenosporium (Diaporthe) species, vermilion species, elsinosporum species, epidermophyton species, pyricularia, erysiphe species (including Compositae powdery mildew (E. Cichorium)), rhizoctonia viticola (Eutypa lata), fusarium species (including Fusarium nii, fusarium graminearum, F. Langoset, fusarium moniliformis, fusarium mucilaginosum, Fusarium solani, fusarium oxysporum, fusarium layering), wheat take-all germ (Gaeumannomyces graminis), gibberella canescens (Gibberella fujikuroi), soot germ (Gloeodes pomigena), pantoea banana anthracis (Gloeosporium musarum), colletotrichum apple anthracis (Glomerella cingulate), grape tee fungus (Guignardia bidwellii), rust fungus of sabina juniper (Gymnosporangium juniperi-virginianae), The plant may be selected from the group consisting of Helminthosporium species, alternaria species, histoplasma species (including histoplasma capsulatum), red line bacteria, leptographium lindbergi, erysiphe capsici (Leveillula taurica) Sphaerotheca pini (Lophodermium seditiosum), sphaerotheca schneideriana (Microdochium nivale), microsporomyces species the species of the genus Streptomyces, the species of the genus Mucor, the species of the genus sphaericus (including sphaerella graminea, the genus sphaerella, Black spot pathogen (m.pomi)), treetoma, picea, paracoccidioidomycosis, penicillium species (including penicillium digitatum, penicillium italicum), genuinensis, downy mildew species (including downy mildew, downy mildew and downy mildew of jowar), downy mildew species, septoria glume, pachyrhizus, phellinus linteus, mulberry Huang Huo wood needle porus (Phellinus igniarus), pinus species, phoma species, phomopsis (Phomopsis viticola) grape phomopsis species (including phytophthora infestans), pinus species (including downy mildew), pinus species (including pinus holos), Grape downy mildew (p.vinicala)), species of the genus alternaria, species of the genus pekoe (including pekoe gracile monocystis (p.leucotrichia), polymyxa graminearum (Polymyxa graminis), polymyxa betana (Polymyxa betae), photinia fraseri (Pseudocercosporella herpotrichoides), species of the genus pseudomonas, species of the genus pseudoperonospora (including pseudoperonospora cucumeria, pseudoperonospora scandens), pseudopeziza tracheiphila, and, The genus Peronospora species (including Hortensis (P.hordei), rhizopus nikoense (P.recondita), rhizopus nikoense (P.Striiformis), rhizopus nikoense (P.triticina)), rhizoctonia species, pyricularia species (including Pyricularia oryzae (P.oryzae)), pythium species (including Pythium ultimum), rhizopus species, rhizoctonia species, rhizopus minutissima (Rhizomucor pusillus), rhizopus arrhizus, rhizopus species (including Saccharopolyspora spinosa and Saccharopolyspora spinosa), rhizopus calis, rhizopus spinosus, rhizopus, Coal spot disease (Schizothyrium pomi), sclerotinia species, sclerotium species, septoria species (including septoria nodorum (S. Nodorum), septoria tritici (S. Tritici)), powdery mildew (Sphaerotheca macularis), single cyst of brown wire (Sphaerotheca fusca) (powdery mildew of cucumber (Sphaerotheca fuliginea)), sporotrichum (Sporothorix) species, septoria nodorum (Stagonospora nodorum), The species of the genus Physiosphaera (Stemphylium), the species of the genus Physiosphaera (Stereum hirsutum), the species of the genus Rhizoctonia (Thanatephorus cucumeris), the species of the genus Leuconostoc (Thielaviopsis basicola), the species of the genus Tilletia, the species of the genus Trichoderma (including Trichoderma harzianum, trichoderma pseudokoningii, trichoderma viride), the species of the genus Phyllostachys, the species of the genus Leuconostoc (Urocystis), the species of the genus Leuconostoc (Ustilago), the species of the genus Armillaria (including Maricoium apple (V.inaequalis)), the species of the genus Armillariella, verticillium species, and xanthomonas species.

The compounds of formula (I) may be used, for example, in lawns, ornamental plants such as flowers, shrubs, hardwood or evergreen plants, for example conifers, as well as tree injection, pest management and the like.

Within the scope of the present invention, the target crop and/or useful plant to be protected typically includes perennial and annual crops, such as berry plants, e.g. blackberry, blueberry, cranberry, raspberry and strawberry; grains such as barley, maize (corn), millet, oat, rice, rye, sorghum, triticale, and wheat; fiber plants, such as cotton, flax, hemp, jute, and sisal; field crops, such as sugar beet and fodder beet, coffee beans, hops, mustard, rape (canola), poppy, sugarcane, sunflower, tea and tobacco, fruit trees, such as apples, apricots, avocados, bananas, cherries, oranges, nectarines, peaches, pears and plums, grasses, such as bermuda grass, bluegrass, bunte grass, ciliate grass, nigella sativa, holy-old-grass and zoysia japonica, herbs, such as basil, borage, chives, coriander, lavender, pubescent angelica, peppermint, oregano, parsley, rosemary, sage and thyme, beans, such as beans, lentils, peas and soybeans, nuts, such as almonds, cashew nuts, groundnuts, hazelnuts, peanuts, pecans, pistachios and walnuts, ornamental plants, such as oil palm, ornamental plants, such as flowers, shrubs and trees, other trees, such as cocoa, coco, trees, and rubber trees, vegetables, such as flowers, lettuce, vegetables, such as potatoes, lettuce, garbanjo, cucurbits, cucumbers, cucurbits, carrots, melons and carrots, potatoes, and potatoes.

The term "useful plant" is to be understood as also including useful plants which are rendered tolerant to herbicides like bromoxynil or classes of herbicides like for example HPPD inhibitors, ALS inhibitors like for example primisulfuron, primisulfuron and trifloxysulfuron, EPSPS (5-enol-acetone-shikimate-3-phosphate-synthase) inhibitors, GS (glutamine synthase) inhibitors or PPO (protoporphyrinogen oxidase) inhibitors as a result of conventional breeding methods or genetic engineering. Examples of crops which have been rendered imidazolinone (e.g. imazethapyr) tolerant by conventional breeding methods (mutagenesis) areSummer rape (Canola). Examples of crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate-and glufosinate-resistant maize varieties that are prepared by AndTrade names are commercially available.

The term "useful plant" is to be understood as also including useful plants which have been so transformed by the use of recombinant DNA technology that they are capable of synthesizing one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus bacillus.

Examples of such plants are: (maize variety, cryIA (b) toxin expression); YIELDGARD (Maize variety, cryIIIB (b 1) toxin expressed); YIELDGARD(Maize varieties expressing CryIA (b) and CryIIIB (b 1) toxins); (maize variety, cry9 (c) toxin expressed); herculex (Maize variety, enzyme phosphinothricin N-acetyltransferase (PAT) expressing CryIF (a 2) toxin and obtaining tolerance to the herbicide glufosinate; (NuCOTN))(Cotton variety, cryIA (c) toxin expressed); bollgard(Cotton variety, cryIA (c) toxin expressed); bollgard(Cotton varieties expressing CryIA (c) and CryIIA (b) toxins); (cotton variety, expressing VIP toxin); (potato variety, expressing CryIIIA toxin); GT ADVANTAGE (GA 21 glyphosate resistance trait), CB Advantage (Bt 11 Corn Borer (CB) trait),RW (corn rootworm trait)

The term "crop" is to be understood as also including crop plants which have been so transformed by the use of recombinant DNA technology to enable synthesis of one or more selectively acting toxins, such toxins being as are known, for example, from toxin-producing bacteria, especially those of the genus bacillus.

Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins from bacillus cereus or bacillus thuringiensis; or insecticidal proteins from bacillus thuringiensis (Bacillus thuringiensis), such as delta-endotoxins, e.g., cry1Ab, cry1Ac, cry1F, cry Fa2, cry2Ab, cry3A, cry Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), e.g., vip1, vip2, vip3 or Vip3A; or insecticidal proteins of nematode-parasitic bacteria, such as the species Photorhabdus (Photorhabdus spp.) or Xenorhabdus (Xenorhabdus spp.), such as the species Photorhabdus (Photorhabdus luminescens), xenorhabdus nematophilus (Xenorhabdus nematophilus); toxins produced by animals, such as scorpions, spider toxins, bee toxins and other insect-specific neurotoxins, toxins produced by fungi, such as streptomycins, phytolectins (lecins), such as pea lectin, barley lectin or galanthamine lectin, lectins (agglutinin), protease inhibitors, such as trypsin inhibitors, silk protease inhibitors, potato glycoproteins, cystatin, papain inhibitors, ribosome Inactivating Proteins (RIP), such as ricin, corn-RIP, abrin, luffa seed toxin, saporin or curcin, steroid metabolizing enzymes, such as 3-hydroxysteroid oxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol oxidase, ecdysone inhibitors, HMG-COA-reductase, ion channel blockers, such as sodium or calcium channel blockers, juvenile hormone esterases, diuretic hormone receptors, stilbene synthase, bibenzyl synthase, ion channel blockers, cholesterol metabolism enzymes, cholesterol-binding-associated with the protein, chitinase and glucanase.

Further, in the context of the present invention, delta-endotoxins (e.g., cry1Ab, cry1Ac, cry1F, cry Fa2, cry2Ab, cry3A, cry Bb1 or Cry 9C) or vegetative insecticidal proteins (Vip) (e.g., vip1, vip2, vip3 or Vip 3A) are understood to obviously also include mixed toxins, truncated toxins and modified toxins. Hybrid toxins are recombinantly produced by a new combination of different domains of those proteins (see, e.g., WO 02/15701). Truncated toxins, such as truncated Cry1 abs, are known. In the case of modified toxins, one or more amino acids of the naturally occurring toxin are replaced. In such amino acid substitutions, it is preferred to insert non-naturally occurring protease recognition sequences into the toxin, such as, for example, in the case of Cry3A055, cathepsin-G-recognition sequences into the Cry3A toxin (see WO 03/018810).

Examples of such toxins or transgenic plants capable of synthesizing such toxins are disclosed, for example, in EP-A-0 374 753, WO 93/07278, WO 95/34656, EP-A-0 427 529, EP-A-451 878 and WO 03/052073.

Methods for preparing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above. CryI-type deoxyribonucleic acids and their preparation are known, for example, from WO 95/34656, EP-A-0 367 474, EP-A-0 401 979 and WO 90/13651.

Toxins contained in transgenic plants render the plants tolerant to harmful insects. Such insects may be present in any insect taxa, but are particularly common in beetles (coleoptera), diptera insects (diptera), and moths (lepidoptera).

Transgenic plants comprising one or more genes encoding insecticide resistance and expressing one or more toxins are known and some of them are commercially available. Examples of such plants are: (maize variety, cry1Ab toxin expressed); YIELDGARD (Maize variety, cry3Bb1 toxin expressed); YIELDGARD(Maize variety, expressing Cry1Ab and Cry3Bb1 toxins); (maize variety, cry9C toxin expressed); herculex (Maize variety, enzyme phosphinothricin N-acetyltransferase (PAT) expressing Cry1Fa2 toxin and obtaining tolerance to herbicide glufosinate; (NuCOTN))(Cotton variety, cry1Ac toxin expressed); bollgard(Cotton variety, cry1Ac toxin expressed); bollgard(Cotton varieties expressing Cry1Ac and Cry2Ab toxins); (cotton variety, expressing Vip3A and Cry1Ab toxins); (potato variety, expressing Cry3A toxin); GT ADVANTAGE (GA 21 glyphosate resistance trait), CB Advantage (Bt 11 Corn Borer (CB) trait) and

Further examples of such transgenic crops are:

Bt11 maize from Zhengda seed company (SYNGENTA SEEDS SAS), huo Bite lines (CHEMIN DEL' Hobit) 27, F-31 790 san Su Weier (St. Sauveur), france accession number C/FR/96/05/10. Genetically modified maize is rendered resistant to attack by european corn borer (corn borer and cnaphalocrocis medinalis) by transgenic expression of truncated Cry1Ab toxins. Bt11 maize also transgenically expresses PAT enzyme to obtain tolerance to the herbicide glufosinate.

Bt176 corn from seed of Fangda, huo Bite, line 27, F-31 790 san Su Weier, france accession number C/FR/96/05/10. Genetically modified maize, genetically expressed as a Cry1Ab toxin, is resistant to attack by european corn borers (corn borers and cnaphalocrocis medinalis). Bt176 maize also transgenically expresses PAT enzyme to gain tolerance to the herbicide glufosinate.

MIR604 corn from seed of Fangda, huo Bite, line 27, F-31 790 san Su Weier, france accession number C/FR/96/05/10. Corn that has been rendered insect-resistant by transgenic expression of the modified Cry3A toxin. The toxin is Cry3A055 modified by insertion of a cathepsin-G-protease recognition sequence. The preparation of such transgenic maize plants is described in WO 03/018810.

MON 863 corn from Monsanto Europe S.A.) 270-272 Teflon (Avenue DE Tervuren), B-1150 Brussels, belgium, accession number C/DE/02/9.MON 863 expresses a Cry3Bb1 toxin and is resistant to certain coleopteran insects.

IPC 531 cotton from Mengshan European company 270-272 Teflon, B-1150 Brussels, belgium under accession number C/ES/96/02.

6.1507 Corn from pioneer overseas company (Pioneer Overseas Corporation), tedelsco, avenue Tedesco, 7B-1160 Brussels, belgium, accession number C/NL/00/10. Genetically modified maize, expressing the protein Cry1F to obtain resistance to certain lepidopterans, and PAT protein to obtain tolerance to the herbicide glufosinate.

NK603×MON 810 maize from Mengshan European company 270-272 Teflon, B-1150 Brussels, belgium under accession number C/GB/02/M3/03. By crossing the genetically modified varieties NK603 and MON 810, it is made up of a conventionally bred hybrid maize variety. NK603×MON 810 maize transgenically expresses the protein CP4 EPSPS obtained from Agrobacterium strain CP4 for herbicide(Containing glyphosate) and also expresses Cry1Ab toxins obtained from bacillus thuringiensis subspecies kurthami, making them resistant to certain lepidopterans, including european corn borer.

The compounds of formula (I) can be used for controlling or preventing phytopathogenic diseases, in particular diseases caused by phytopathogenic fungi, such as Botrytis cinerea (Botrytis cinerea) on rosaceae, vitaceae, solanaceae, cucurbitaceae and Leguminosae, callicarpae (Glomerella lagenarium) on Cucurbitaceae, leguminosae, brassicaceae and Compositae, for example, sclerotinia sclerotiorum on soybean, rape and sunflower, solanaceae such as Alternaria solani on tomato and potato, clostridium cinum (Monographella nivalis) on Graminearum, rhizoctonia cerealis (Pyrenophora teres) on Gramineae such as barley, and Clostridium graminearum (Mycosphaerella graminicola) on wheat.

As used herein, the term "locus" means a place in or on which plants are grown, or where seeds of cultivated plants are sown, or where seeds are to be placed in soil. It includes soil, seeds, and seedlings, along with established vegetation.

The term "plant" refers to all the tangible parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, leaves, and fruits.

The term "plant propagation material" is understood to mean reproductive parts of plants, such as seeds, which parts can be used for propagation of plants, as well as nutritional materials, such as cuttings or tubers (e.g. potatoes). Mention may be made, for example, of seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes and parts of plants. Germinated plants and young plants to be transplanted after germination or after emergence can also be mentioned. These young plants may be protected prior to transplantation by being treated, either completely or partially, by dipping. Preferably, "plant propagation material" is understood to mean seeds.

The compounds of formula (I) can be used in unmodified form or, preferably, together with adjuvants conventionally used in the field of formulation. For this purpose, they can be conveniently formulated in a known manner as emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions or suspensions, diluted emulsions, wettable powders, soluble powders, dusts, granules and also encapsulates, for example in polymeric substances. For the type of composition, the method of application is selected according to the intended purpose and the circumstances at the time, such as spraying, atomizing, dusting, broadcasting, painting or pouring. The composition may also contain further adjuvants, such as stabilizers, defoamers, viscosity modifiers, binders or tackifiers, together with fertilizers, micronutrient donors or other formulations for achieving special effects.

Suitable carriers and adjuvants, for example for agricultural use, may be solid or liquid and are substances useful in formulation technology, for example natural or regenerated mineral substances, solvents, dispersions, wetting agents, tackifiers, thickeners, binders or fertilisers. Such vectors are described, for example, in WO 97/33890.

Suspension concentrates are aqueous formulations in which finely divided solid particles of the active compound are suspended. Such formulations comprise anti-settling agents and dispersants, and may further comprise wetting agents to enhance activity, as well as defoamers and crystal growth inhibitors. In use, these concentrates are diluted in water and typically applied as a spray to the area to be treated. The amount of active ingredient may range from 0.5% to 95% of the concentrate.

Wettable powders are in the form of finely divided particles which are readily dispersible in water or other liquid carrier. These particles contain the active ingredient retained in a solid matrix. Typical solid matrices include fuller's earth, kaolin clays, silica and other readily wettable organic or inorganic solids. Wettable powders normally contain from 5% to 95% of the active ingredient plus a small amount of wetting, dispersing or emulsifying agents.

Emulsifiable concentrates are homogeneous liquid compositions dispersible in water or other liquids and may consist entirely of the active compound with a liquid or solid emulsifier, or may also contain liquid carriers such as xylene, heavy aromatic naphthas, isophorone and other non-volatile organic solvents. In use, these concentrates are dispersed in water or other liquid and are typically applied as a spray to the area to be treated. The amount of active ingredient may range from 0.5% to 95% of the concentrate.

The granule formulation includes both extrudates and coarser particles and is typically applied to the area in need of treatment without dilution. Typical carriers for particulate formulations include sand, fuller's earth, attapulgite clay, bentonite, montmorillonite, vermiculite, perlite, calcium carbonate, brick, pumice, pyrophyllite, kaolin, dolomite, stucco, wood flour, crushed corn cobs, crushed peanut shells, sugar, sodium chloride, sodium sulfate, sodium silicate, sodium borate, magnesium oxide, mica, iron oxide, zinc oxide, titanium oxide, antimony oxide, cryolite, gypsum, diatomaceous earth, calcium sulfate and other organic or inorganic absorbent active compounds or materials that may be coated with an active compound. The particulate formulations typically contain from 5% to 25% of active ingredients which may include surfactants such as heavy aromatic naphthas, kerosene and other petroleum fractions, or vegetable oils, and/or binders such as dextrins, gums or synthetic resins.

Dust is a free-flowing mixture of the active ingredient with finely divided solids such as talc, clay, flour and other organic and inorganic solids as dispersants and carriers.

Microcapsules are typically droplets or particles of an active ingredient enclosed within an inert porous shell that allows the enclosed material to escape to the environment at a controlled rate. The diameter of the encapsulated droplets is typically 1 to 50 microns. The encapsulated liquid typically comprises 50% to 95% by weight of the capsule and may contain a solvent in addition to the active compound. The encapsulated particles are typically porous particles, wherein the porous membrane seals the particle orifice, retaining the active species in liquid form inside the particle pores. The diameter of the particles typically ranges from 1mm to 1 cm and preferably from 1mm to 2 mm. The particles are formed by extrusion, agglomeration or spheronization, or are naturally occurring. Examples of such materials are vermiculite, sintered clay, kaolin, attapulgite clay, sawdust and carbon fines. Shell or membrane materials include natural and synthetic rubbers, fibrous materials, styrene-butadiene copolymers, polyacrylonitriles, polyacrylates, polyesters, polyamides, polyureas, polyurethanes and starch xanthates.

Other useful formulations for agrochemical applications include simple solutions of the active ingredient in solvents such as acetone, alkylated naphthalenes, xylenes and other organic solvents in which the active ingredient is fully dissolved at the desired concentration. Pressurized sprays can also be used wherein the active ingredient is dispersed in finely divided form as a result of evaporation of the low boiling dispersant solvent carrier.

Suitable agricultural adjuvants and carriers useful in formulating the compositions of the invention in the above formulation types are well known to those skilled in the art.

Liquid carriers which may be used include, for example, water, toluene, xylene, naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, acetic anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, chlorobenzene, cyclohexane, cyclohexanol, alkyl acetate, diacetone alcohol, 1, 2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol rosin acid, diethylene glycol butyl ether, diethylene glycol diethyl ether, diethylene glycol methyl ether, N, N-dimethylformamide, dimethyl sulfoxide, 1, 4-dioxane, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, dipropylene glycol (diproxitol), alkylpyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1-trichloroethane, 2-heptanone, alpha-pinene, alpha-methyl acetate, alpha-ethyl acetate, alpha-methyl acetate, beta-ethyl acetate, beta-methyl acetate, beta-methyl acetate, beta d-limonene, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol diacetate, glycerol monoacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, cumene, isopropyl alcohol, ethyl alcohol, butyl alcohol, isopropyl alcohol, d-limonene, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol diacetate, glycerol monoacetate triacetin, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, cumene, butyl acetate, methanol, ethanol, isopropanol, and higher molecular weight alcohols such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, and the like, ethylene glycol, propylene glycol, glycerol, and N-methyl-2-pyrrolidone. Water is typically the carrier of choice for dilution of the concentrate.

Suitable solid carriers include, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, diatomaceous earth (kieselguhr), chalk, diatomaceous earth (diatomaxeous earth), lime, calcium carbonate, bentonite, fuller's earth, cotton seed hulls, wheat flour, soybean flour, pumice, wood flour, walnut hull flour, and lignin.

A wide range of surfactants can be advantageously employed in the liquid and solid compositions, particularly those designed to be diluted with carrier prior to application. These agents, when used, typically comprise from 0.1% to 15% by weight of the formulation. They may be anionic, cationic, nonionic or polymeric in nature and may be employed as emulsifiers, wetting agents, suspending agents or for other purposes. Typical surfactants include alkyl sulphates such as diethanolammonium lauryl sulphate, alkylaryl sulphonates such as calcium dodecyl benzene sulphonate, alkylphenol-alkylene oxide adducts such as nonylphenol-C.sub.18 ethoxylate, alcohol-alkylene oxide adducts such as tridecyl alcohol-C.sub.16 ethoxylate, soaps such as sodium stearate, alkyl naphthalene sulphonates such as sodium dibutyl naphthalene sulphonate, salts of dialkyl sulphosuccinates such as sodium di (2-ethylhexyl) sulphosuccinate, sorbitol esters such as sorbitol oleate, quaternary amines such as lauryl trimethyl ammonium chloride, polyethylene glycol esters of fatty acids such as polyethylene glycol stearate, block copolymers of ethylene oxide and propylene oxide, and salts of mono-and dialkyl phosphates.

Other adjuvants commonly used in agricultural compositions include crystallization inhibitors, viscosity modifiers, suspending agents, spray droplet modifiers, pigments, antioxidants, foaming agents, defoamers, opacifiers, compatibilizing agents, defoamers, masking agents, neutralizing agents and buffering agents, corrosion inhibitors, dyes, odorants, spreading agents, penetration aids, micronutrients, emollients, lubricants, and fixing agents.

Furthermore, further biocidal active ingredients or compositions may be combined with the compositions of the present invention and used in the methods of the present invention and administered simultaneously or sequentially with the compositions of the present invention. When administered simultaneously, these additional active ingredients may be formulated or mixed together with the compositions of the present invention, for example, in a spray can. These additional biocidal active ingredients can be fungicides, herbicides, insecticides, bactericides, acaricides, nematicides and/or plant growth regulators.

The pesticides mentioned herein using their common names are, for example, known from "THE PESTICIDE Manual of pesticides", 15 th edition, british crop protection committee (British Crop Protection Council) 2009.

In addition, the compositions of the present invention may also be administered with one or more systemic acquired resistance inducers ("SAR" inducers). SAR inducers are known and described, for example, in U.S. patent No. US 6,919,298 and include, for example, salicylates and the commercial SAR inducer alamic benzene-S-methyl.

The compounds of formula (I) are generally used in the form of agrochemical compositions and can be applied simultaneously or sequentially with further compounds to the crop area or plant to be treated. For example, these additional compounds may be fertilizers or micronutrient donors or other formulations that affect plant growth. They may also be selective or nonselective herbicides, together with insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or adjuvants which facilitate application, which are customarily used in the art of formulation.

The compounds of formula (I) may be used in the form of compositions for controlling or protecting against phytopathogenic microorganisms, comprising as active ingredient at least one compound of formula (I) or at least one preferred individual compound as defined herein, in free form or in agrochemically usable salt form, and at least one of the above-mentioned adjuvants.

The present invention therefore provides a composition, preferably a fungicidal composition, comprising at least one compound of formula (I), an agriculturally acceptable carrier and optionally adjuvants. An agriculturally acceptable carrier is, for example, a carrier suitable for agricultural use. Agricultural vectors are well known in the art. Preferably, the composition may comprise, in addition to the compound having formula (I), at least one or more pesticidally active compounds, for example an additional fungicidally active ingredient.

The compound of formula (I) may be the only active ingredient of the composition or it may be admixed with one or more additional active ingredients such as pesticides, fungicides, synergists, herbicides or plant growth regulators, as appropriate. In some cases, additional active ingredients may produce unexpected synergistic activity.

Examples of suitable additional active ingredients include acyclic amino acid (acycloamino acid) fungicides, aliphatic nitrogen fungicides, amide fungicides, aniline fungicides, antibiotic fungicides, aromatic fungicides, arsenic-containing fungicides, aryl phenyl ketone fungicides, benzamide fungicides, benzanilide fungicides, benzimidazole fungicides, benzothiazole fungicides, plant fungicides, bridged biphenyl fungicides, carbamate fungicides, benzoate fungicides, conazole fungicides, copper fungicides, dicarboximide fungicides, dinitrophenol fungicides, dithiocarbamate fungicides, dithiolane fungicides, furamide fungicides, furfuryl amine fungicides, hydrazide fungicides, imidazole fungicides, mercury fungicides, morpholine fungicides, organophosphorus fungicides, organotin fungicides, oxathiamine (oxathiin) fungicides, oxazole fungicides, phenylsulfamide fungicides, polysulfide fungicides, pyrazole fungicides, pyridine fungicides, pyrimidine fungicides, pyrrole fungicides, quaternary ammonium fungicides, quinoline fungicides, quinone fungicides, quinoxaline fungicides, strobilurin fungicides, sulfonamide (sulfonanilide) fungicides, thiadiazole fungicides, thiazole, thiazolidine fungicides, thiocarbamate fungicides, triazole fungicides, 35, and valium fungicides.

Specific examples of suitable additional active ingredients also include compounds selected from the group consisting of petroleum, 1-bis (4-chlorophenyl) -2-ethoxyethanol, 2, 4-dichlorophenyl benzenesulfonate, 2-fluoro-N-methyl-N-1-naphthacene amide, 4-chlorophenyl phenyl sulfone, acetylchlorfenapyr, aldicarb, methidathion, methoprene (amidothioate), azaphos, hydrocortisone oxalate, amitraz, acaricide, arsenic trioxide, azobenzene, azophos, benomyl, benno Sha Lin (benoxafos), benzyl benzoate, bixafen, deltamethrin, bromacil, bromacillin, Bromethion, bromacil, buprofezin, pyrifos (calcium polysulfide), toxafen, clofenamate, carbothion, cycloimidazole, fenamic mefenamate (chlorbenside), acetamiprid hydrochloride, fenamidone (chlorfenson), fenamidone (chlorfensulfide), ethylfenamidone (chlorobenzilate), itomine (chloromebuform), chlorfenapyr (chloromethiuron), Propyl ester acaricidal alcohol (chloropropylate), chlorfenphos (chlorthiophos), guathrin (cinerin) I, guathrin II, guathrin (cinerins), chlorocyanioside (closantel), coumaphos (coumaphos), clomiphos (crotamiton), coumaphos (crotoxyphos), thiazate, carprofen (cyanthoate), DCPM, DDT, trifluophos (demephion), trifluophos-O, trifluophos-S, methyl endophos, Neoprene-O, methylNeoprene-O, neoprene-S, methylNeoprene-S, sulfofos (demeton-S-methylsulfon), dichlorvos (dicyclophos), defenphos, methylflophos (dimefox), defenpyroxim (dinex), defenpyroxim (dinex-diclexine), defenproxil (dinocap) -4, defenprox-6, dinitrate, nitroselate (dinopenton), nitrooctyl (dinosulfon), nitrobutyl (dinoterbon), pyrophos (Amersham), Dirofloxacin, diphenylsulfone, disulfiram, DNOC, phenoxypropargite (dofenapyn), doramectin, clomazone (endothion), epstein (eprinomectin), YISHIGU (ethoate-methyl), ethirimos (etrimfos), anti-mite (fenazaflor), phenylbutazone (fenbutatin oxide), benfuracarb (fenothiocarb), fenpyrad, fenpyroximate (fenpyroximate), fenpyrazamine (fenpyrazamine), fenpropidin (fenson), flunifedipine (fentrifanil), fenpyrazamine (flubenzimine), flufenuron, bifenox (fluenetil), flufenpyrad (fluorbenside), FMC 1137, valicarb hydrochloride, methomyl (formparanate), gamma-HCH, valicarb, fenpyroximate, cetyl cyclopropanecarboxylate, fenpyrad, jasmine I, jasmine II, iodiphos, lindane, propargite, chlorpyrifos, Aphphos, dithiine, methifen, chlorfenphos, methyl bromide, methomyl, fenoxycarb, milbexime, propylenefluoride, monocrotophos, locarban, moxidectin, dibromophosphorus (naled), 4-chloro-2- (2-chloro-2-methyl-propyl) -5- [ (6-iodo-3-pyridinyl) methoxy ] pyridazin-3-one, flumetsulam, nikkomycin, pentafencarb 1:1 zinc chloride complex, omethoate, phosphorous sulfenphos, phorin, pp' -DDT, parathion, permethrin, fenthion, valinate, thiocyclophos, phospham, turpentine (polychloroterpenes) chloride, Acaricide (polynactins), prochloraz, chlorpyrifos, propoxur, ethionamide, fosthiazate, pyrethrin I, pyrethrin II, pyrethrin, pyridaphethione, pyrithione, quinophos (quinalphos), quinophos (quintiofos), R-1492, glycifos, rotenone, octophos, captan, selacin, su Liu phosphorus, SSI-121, shu Feilun, flufenamid, thiotepa, sulfur, flufenazine, tau-fluvalinate, TEPP, terbucarb, tetramat, flufenitrothion, thiafenox, indoxacarb, monocyclocarb, tebufenpyrad, Methyl etoposide, g-miticide, threomycin, weijunos, benomyl, triazophos, triazuron, triclopyr, triazocine, triazuron, methimazole (vaniliprole), baishaxin (bethoxazin), copper dioctate, copper sulfate, cybutryne, dichlornaphthaquinone, dichlorophenol, chlorphenamine, triton, slaked lime, mancozeb, chloranil, quinine, tin triphenylacetate, tin triphenylhydroxide, fosetyl, piperazine, thiophanate, chloral sugar, becfos, pyridin-4-amine, strychnine, 1-hydroxy-1H-pyridine-2-thione, 4- (quinoxalin-2-ylamino) benzenesulfonamide, 8-hydroxyquinoline sulfate, bronitol, copper hydroxide, cresol, pyrithione, duodesine, sodium disultone, formaldehyde, mercuric oxide, kasugamycin hydrochloride hydrate, nickel bis (dimethyldithiocarbamate), trichloromethyl pyridine, xin Saitong, oxolinic acid, terramycin, potassium hydroxyquinoline sulfate, thiabendazole, streptomycin sesquisulfate, leaf-cumyl phthalein, thimerosal, cotton brown moth GV, agrobacterium radiobacter, amblyseius species (Amblyseius spp.), apidae NPV, primrose wing wasp (Anagrus atomus), Short-distance aphid (Aphelinus abdominalis), cotton aphid parasitic wasp (Aphidius colemani), aphid eating gall midge (Aphidoletes aphidimyza), alfalfa silver vein noctuid NPV, bacillus sphaericus (Bacillus sphaericus Neide), beauveria bassiana (Beauveria brongniartii), common green lacewing (Chrysoperla carnea), cryptolipa mansoni (Cryptolaemus montrouzieri), and, Cyrtosis pomonella GV, siberia off-jaw cocoon bee (Dacnusa sibirica), pisum sativum lirio She Yingji wasp (Diglyphus isaea), aphis citri (Eretmocerus eremicus), heterodera mobilis (Heterorhabditis bacteriophora) and Heterodera grandis (H.megdis), ladybug (Hippodamia convergens), trigonella citrifolia parasitic wasp (Leptomastix dactylopii), Plant bug (Macrolophus caliginosus), cabbage looper NPV, huang Kuobing flea wasp (Metaphycus helvolus), metarhizium anisopliae (Metarhizium anisopliae var. Acridum), metarhizium anisopliae microsporidianum variant (Metarhizium anisopliae var. Aniopliae), european pine needle (Neodiprion sertifer) NPV and red head pine needle (N.lecontei) NPV, The plant species of the genus orius, paecilomyces fumosoroseus (Paecilomyces fumosoroseus), physciulus wisconsii (Phytoseiulus persimilis), mao Wen nematodes (STEINERNEMA BIBIONIS), spodoptera frugiperda (STEINERNEMA CARPOCAPSAE), spodoptera exigua, grignard nematodes (STEINERNEMA GLASERI), nematoda aculeata (STEINERNEMA RIOBRAVE), nematoda (STEINERNEMA RIOBRAVIS), gryllotalpa nematodes (STEINERNEMA SCAPTERISCI), steinernema spp, trichogramma, xiekola (Typhlodromus occidentalis), verticillium lecanii (Verticillium lecanii), zophos (apholate), bis (aziridine) methylaminophosphine sulfide (bisazir), busulfan, dimetif (dimatif), altretamine (hemel), hexamethonium (hempa), methyl aldicarb (metepa), methyl thiaaldicarb (methiotepa), methyl azolphoszine (methyl apholate), infertility (morzid), fluvaluron (penfluron), aldicarb (tepa), thiohexa-methyl phosphate (thiohempa), thiaaldicarb, trolamine, urethane imine acetate, (E) -dec-5-en-1-yl ester with (E) -dec-5-en-1-ol, acetic acid (E) -tridec-4-en-1-yl ester, (E) -6-methylhept-2-en-4-ol, acetic acid (E, Z) -tetradeca-4, 10-dien-1-yl ester, (Z) -dodecan-7-en-1-yl acetate, (Z) -hexadeca-11-enal, acetic acid (Z) -hexadeca-11-en-1-yl ester, acetic acid (Z) -hexadeca-13-en-11-yn-1-yl ester, (Z) -eicosan-13-en-10-one, (Z) -tetradeca-7-en-1-al, (Z) -tetradeca-9-en-1-ol, acetic acid (Z) -tetradeca-9-en-1-yl ester, acetic acid (7E, 9Z) -dodecan-7, 9-dien-1-yl ester, acetic acid (9Z, 11E) -tetradeca-9, 11-dien-1-yl ester, acetic acid (9Z, 12E) -tetradeca-9, 12-dien-1-yl ester, 14-methyl octadec-1-ene, 4-methyl non-5-ol and 4-methyl non-5-one, alpha-polylysine, western pine bark beetle aggregate pheromone, dodecadienol (codlelure), available Mongolian (codlemone), lure ketone (cuelure), epoxy nonadecane, dodeca-8-en-1-yl acetate, dodeca-9-en-1-yl acetate, dodeca-8, 10-diene-1-yl acetate, bark beetle attractant (dominicalure), 4-methyl ethyl octoate, eugenol, southern pine bark beetle aggregate pheromone (front), A trapping and killing alkene mixture (grandlure), a trapping and killing alkene mixture I, a trapping and killing alkene mixture II, a trapping and killing alkene mixture III, a trapping and killing alkene mixture IV, a trapping agent (hexalure), bark beetle dienol (ipsdienol), small panol (ipsenol), a tortoise sex attractant (japoniure), trimethyl dioxytricyclononane (lineatin), a noctuid attractant (litlure), a noctuid sex attractant (looplure), trapping and killing ester (medlure), megatomoic acid, a trap ether (methyl eugenol), Insect attractant (muscalure), octadeca-2, 13-dien-1-yl acetate, octadeca-3, 13-dien-1-yl acetate, he Kangbi (orfraure), cocois Rhinocerotis cinerea aggregation pheromone (oryctalure), feverfew (otrimone), triclopyr (siglure), sordidn, edible fungus methyl attractant (sulcatol), tetradeca-11-en-1-yl acetate, mediterranean fruit fly attractant (trimedlure), mediterranean fruit fly attractant A, mediterranean fruit fly attractant B1, and, The insect attractant B2, the insect attractant C, trunc-call, 2- (octylthio) ethanol, the mosquito repellent ketone (butopyronoxyl), the butoxy (polypropylene glycol), the dibutyl adipate, the dibutyl phthalate, the dibutyl succinate, the mosquito repellent amine, the mosquito repellent (dimethylcarbate), the dimethyl phthalate, the ethylhexyl glycol, the hexaurea (hexamide), the mequindine (methoquin-butyl), the methyl neodecanoamide (methylneodecanamide), the oxamate (oxamate), Pai-kariding (picaridin), 1-dichloro-1-nitroethane, 1-dichloro-2, 2-bis (4-ethylphenyl) ethane, 1, 2-dichloropropane and 1, 3-dichloropropene, 1-bromo-2-chloroethane, 2-trichloro-1- (3, 4-dichlorophenyl) ethyl acetate, 2-ethylsulfinylethylmethylphosphonate 2, 2-dichloroethylene, 2- (1, 3-dithiolane-2-yl) phenyl dimethylcarbamate, 2- (2-butoxyethoxy) ethyl thiocyanate, 2- (4, 5-dimethyl-1, 3-dioxolan-2-yl) phenyl methylcarbamate, 2- (4-chloro-3, 5-xylyloxy) ethanol, 2-chlorovinyldiethyl phosphate, 2-imidazolidinone, 2-isovalerylindan-1, 3-dione, 2-methyl (prop-2-ynyl) aminophenyl methylcarbamate, 2-thiocyanoethyl laurate, 3-bromo-1-chloropro-1-ene, 3-methyl-1-phenylpyrazol-5-yl dimethylcarbamate, 4-methyl (prop-2-ynyl) amino-3, 5-xylyl methylcarbamate, 5-dimethyl-3-oxocyclohex-1-enyl dimethylcarbamate, acephate, acrylonitrile, an airy agent, Alomicin, carboxin, alpha-ecdysone, aluminum phosphide, methomyl, neonicotinoid, methidathion (athidathion), picoline, bacillus thuringiensis delta-endotoxin, barium hexafluorosilicate, barium polysulfide, fumigating pyrethrin, bayer 22/190, bayer 22408, beta-cyhalothrin, pencycurin (bioethanomethrin), biothrin, bis (2-chloroethyl) ether, borax, bromophenaphos, bromo-DDT, carboxin, benflumetofen, terfenaphos (butathiofos), butyl phosphorus, calcium arsenate, Calcium cyanide, carbon disulfide, carbon tetrachloride, bardan hydrochloride, siraidine (cevadine), borneol, chlordane, decachlorone, chloroform, chlorpyrifos, chlorpyrad (chlorprazophos), cis-bifenthrin (cis-resmethrin), cis-bifenthrin (cismethrin), fenvalerate (clocythrin) (alias), copper acetylarsenite, copper arsenate, copper oleate, benfofos (coumithoate), cryolite, CS 708, benazel phosphorus, cartap, cyclofenitrothion, acephate, d-tetramethrin, fenpropion, DAEP, dazomet, desmethyl carbofuran (decarbofuran), desmethyl (diamidafos), triclopyr, desmopressin, dicresyl, dicyclanil, dieldrin, 5-methylpyrazol-3-yl diethyl phosphate, pantopril (dior), tefluthrin, dimchip, permethrin, methylparaben, benomyl, prochloraz, penta, dil, benomyl, vegetable and fruit phosphorus, thiopyran phosphorus, DSP, ecdysterone, EI 1642, EMPC, EPBP, etaphos, ethionine, ethyl formate, dibromoethane, dichloroethane, ethylene oxide, EXD, coumaphos, benfuracarb, fenitrothion, oxazamide (fenoxacrim), pyrifos, fenitrothion, ethylbenfop-ethyl, fluclobinon (flucofuron), benfofos, fos-methyl, benfuracarb, anti-pyrethrin, guazatine acetate, sodium tetrathiocarbonate, benfuracarb (halfenprox), HCH, HEOD, heptachlor, fashion, HHDN, hydrogen cyanide, quinoline carb, IPSP, chlorzophos, carbochlorpyrim, isoxaprop, iso Liu Lin, transplanting agent, isoprothiolane, oxazophos, juvenile hormone I, juvenile hormone II, Juvenile hormone III, chlorpenyl, eneyne, lead arsenate, bromophos, acetamiprid, fosthiazate, m-isopropylphenyl methyl carbamate, magnesium phosphide, azido, methylparaben, aphphos, mercurous chloride, methiphos, metam potassium, metam sodium, methylsulfonyl fluoride, butenamine phosphorus, methoprene, methothrin, methoxam, methyl isothiocyanate, methyl chloroform, methylene chloride, oxadiazon, imazalil, nepeptid, naphthalene, NC-170, nicotine sulfate, nitenpyram, prim, O-ethyl thiophosphonate O-5-dichloro-4-iodophenyl ester, O-4-methyl-2-oxo-2H-benzopyran-7-yl thiophosphonate O, O-diethyl ester, O-6-methyl-2-propylpyrimidin-4-ylsulfophonate O, O-diethyl ester, dithiopyrophosphoric acid O, O, O ', O' -tetrapropyl ester, oleic acid, p-dichlorobenzene, methylparathion, pentachlorophenol, pentachlorolaurate, PH 60-38, fenthion, p-chlorothiophosphate, phosphine, methylphosphine, methamidophos, polychlorinated dicyclopentadiene isomers, potassium arsenite, potassium thiocyanate, precocin I, precocin II, precocin III, amidephyriphos, profenothrin, mefenamic, propylthiophos, pirfenphos, antichlorethamate, quassia extract (quassia), quinalphos-methyl, Livestock phosphorus, iodosalidine, bifenthrin, rotenone, thienyl, rynthrin, rimidine, sabatron (sabadilla), octamethiphos, captan, SI-0009, thiopropionitrile, sodium arsenite, sodium cyanide, sodium fluoride, sodium hexafluorosilicate, sodium pentachlorophenol, sodium selenate, sodium thiocyanate, sulfometuron (sulcofuron), sulfometuron sodium salt (sulcofuron-sodium), sulfuryl fluoride, thiopropate, tar, thiamethoxam, TDE, butyl pyrimidine phosphorus, dithiophosphate, cycloprothrin, tetrachloroethane, ticlophos, thiocyclam oxalate, benomyl, chlorpyrifos, monosultap, tetrabromothrin, antichlorethamate, triazamate, iprovalicarb, clomazone-3, chlorpyrifos, methomyl, triflumuron (tolprocarb), chlorpyrifos, methoprene, veratrine, XMC, zetamethrin, zinc phosphide, tolfenpyr, and halothrin, tefluthrin, bis (tributyltin) oxide, bromoacetamide, ferric phosphate, niclosamide-ethanolamine, tributyltin oxide, pyrimorph, snail, 1, 2-dibromo-3-chloropropane, 1, 3-dichloropropene, 3, 4-dichlorotetrahydrothiophene 1, 1-dioxide, 3- (4-chlorophenyl) -5-methyl rhodamine, triadimefon, 5-methyl-6-thio-1, 3, 5-thiadiazin-3-yl acetic acid, 6-isopentenyl aminopurine, fluorophenyladenine (anisiflupurin), benzothiaz (benclothiaz), cytokinin, DCIP, furfural, isoamidophosphorus (isamidofos), kinetin, verruca verrucosa composition, tetrachlorothiophene, xylenol, zeatin, potassium ethylxanthate, alac-type benzene-S-methyl, giant knotweed (Reynoutria sachalinensis) extract, alpha-chlorohydrin, antuol, barium carbonate, Bismurine urea, bromomurine, bromodiuron, bromomurine amine, chloromurine ketone, cholecalciferol, chlorowarfare, clomequintocet, naphthyridine, pyrimidone, murinone, thiabendazole, diphacinone, calciferol, fluvalinate, fluoroacetamide, flupridine hydrochloride, raterone, phospine, phosphorus, raticide, valinate, chives glucoside, sodium fluoroacetate, thallium sulfate, warfare, 2- (2-butoxyethoxy) ethyl piperonyl ester, 5- (1, 3-benzodioxol-5-yl) -3-hexyl cyclohex-2-enone, farnesol with nerolidol, synergistic ether, MGK 264/synergistic ether, synergistic aldehyde, synergistic ester (propylisomer), S421, synergistic powder, sesamin (sesasmolin), sulfoxide, anthraquinone, copper naphthenate, copper king, dicyclopentadiene, celen, zinc naphthenate, ziram, clothes Ma Ning, ribavirin, chloroindole hydrazide (chloroinconazide), mercuric oxide, thiophanate methyl, azaconazole, bitertanol, furfuryl azole, cyproconazole, difenoconazole, diniconazole, epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, furazolidone, hexaconazole, imazalil, myclobutanil, ipconazole, metconazole, myclobutanil, pyrifos, penconazole, prothioconazole, pyripyroxime (pyrifenox), Prochloraz, propiconazole, cyprodinil, simeconazole (simeconazole), tebuconazole, triflumizole, triazolone, triadimenol, triflumizole, triticonazole, pyrimidol, chloropyrimol, flubenyrimol, bupirimate (bupirimate), methyidine (dimethirimol), ethirimol (ethirimol), dodine, fenpropidin (fenpropidin), fenpropimorph, spiroxamine, tridemorph, cyprodinil, pyrimethanil (pyrimethanil), fenpiclonil, fludioxonil, benalaxyl (benalaxyl), furalaxyl (furalaxyl), metalaxyl, R-metalaxyl, furalamide, oxadixyl (oxadixyl), carbendazim, prochloraz (debacarb), fuberidazole, thiobendazole, ethiprole (chlorzolate), sclerotinia (dichlozoline), tolfenpyr (myclozoline), procymidone (procymidone), ethephon (vinclozoline), boscalid (boscalid), carboxin, formamide, fluoroamide (flutolanil), mechloraz, fenpropidium, prochloraz, and other drugs, Carboxin, penthiopyrad (penthiopyrad), thifluzamide, docusan, biguanide octylamine, and azoxystrobin, dimoxystrobin, enestroburin (Enestrobulin) azoxystrobin, dimoxystrobin, and other drugs enestroburin (enestroburin), and the like pyraclostrobin, thiram, mancozeb, maneb, metiram zineb, captan, zofurben, folpet zineb, captan zofura, folpet, Methylclofos, dichlormid, benthiavalicarb, blasticidin (blasticidin) -S, dimetofen (chloroneb), chlorothalonil, cyflufenamid, cymoxanil, cyclobutrifluram, dicyclofenamid (diclocymet), pyridaben (dichlormazine), chloronitenpyram (dicloran), diethofencarb (diethofencarb), dimethomorph, flumorph, dithianon (dithianon), ethaboxam (ethaboxam), hymexazol (etridiazole), triflumizole, Famoxadone, fenamidone (fenamidone), fenoxanil (fenoxanil), azoxystrobin (ferimzone), fluazinam (fluazinam), flumetylsulforim, fluopicolide (fluopicolide), fluoxytioconazole, sulfenamid (flusulfamide), fluxapyroxad, cyproconazole, fosetyl-aluminum (fosetyl-aluminium), hymexazol (hymexazol), propineb, triazophos (cyazofamid), Sulfofibril (methasulfocarb), benomyl, pencycuron (pencycuron), phthalide, polyoxin (polyoxins), propamocarb (propamocarb), pirfencarb, iodoquinazolinone (proquinazid), fluquinlone (pyroquin), pyripyropene, quinoxyfen, pentachloronitrobenzene, tiadinil, imidazosin (triazoxide), tricyclazole, zinamin, validamycin, valin, zoxamide (zoxamide), mandipropamid (mandipropamid), flubeneteram, isopyrazam, penflufen (sedaxane), benzovindiflupyr, fluxapyroxad hydroxylamine, 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (3 ',4',5' -trifluoro-biphenyl-2-yl) -amide, ipflupyraclostrobin (isoflucypram), isothiabendamine, dipymetitrone, 6-ethyl-5, 7-dioxo-pyrrolo [4,5] [1,4] dithiazolo [1,2-c ] isothiazole-3-carbonitrile, 2- (difluoromethyl) -N- [ 3-ethyl-1, 1-dimethyl-indan-4-yl ] pyridine-3-carboxamide, 4- (2, 6-difluorophenyl) -6-methyl-5-phenyl-pyridazine-3-carbonitrile, (R) -3- (difluoromethyl) -1-methyl-N- [1, 3-trimethylindan-4-yl ] pyrazole-4-carboxamide, 4- (2-bromo-4-fluoro-phenyl) -N- (2-chloro-6-fluoro-phenyl) -2, 5-dimethyl-pyrazol-3-amine, 4- (2-bromo-4-fluorophenyl) -N- (2-chloro-6-fluorophenyl) -1, 3-dimethyl-1H-pyrazol-5-amine fluindapyr, azoxystrobin (jiaxiangjunzhi), lvbenmixianan, dichlobentiazox, mandsbine (mandestrobin), 3- (4, 4-difluoro-3, 4-dihydro-3, 3-dimethylisoquinolin-1-yl) quinolone, 2- [ 2-fluoro-6- [ (8-fluoro-2-methyl-3-quinolinyl) oxy ] phenyl ] propan-2-ol, thiapiprazole (oxathiapiprolin), N- [6- [ [ [ (1-methyltetrazol-5-yl) -phenyl-methylene ] amino ] oxymethyl ] -2-pyridinyl ] carbamic acid tert-butyl ester, pyraziflumid, inpyrfluxam, trolprocarb, chlorofluoroethereal zole, ipfentrifluconazole, 2- (difluoromethyl) -N- [ (3R) -3-ethyl-1, 1-dimethyl-indan-4-yl ] pyridine-3-carboxamide, N '- (2, 5-dimethyl-4-phenoxy-phenyl) -N-ethyl-N-methyl-formamidine, N' - [4- (4, 5-dichlorothiazol-2-yl) oxy-2, 5-dimethyl-phenyl ] -N-ethyl-N-methyl-formamidine, [2- [3- [2- [1- [2- [3, 5-bis (difluoromethyl) pyrazol-1-yl ] acetyl ] -4-piperidinyl ] thiazol-4-yl ] -4, 5-dihydroisoxazol-5-yl ] -3-chloro-phenyl ] methanesulfonate, But-3-ynyl N- [6- [ [ (Z) - [ (1-methyltetrazol-5-yl) -phenyl-methylene ] amino ] oxymethyl ] -2-pyridinyl ] carbamate, methyl N- [ [5- [4- (2, 4-dimethylphenyl) triazol-2-yl ] -2-methyl-phenyl ] methyl ] carbamate, 3-chloro-6-methyl-5-phenyl-4- (2, 4, 6-trifluorophenyl) pyridazine, pyridachlometyl, 3- (difluoromethyl) -1-methyl-N- [1, 3-trimethylindan-4-yl ] pyrazole-4-carboxamide, 1- [2- [ [1- (4-chlorophenyl) pyrazol-3-yl ] oxymethyl ] -3-methyl-phenyl ] -4-methyl-tetrazol-5-one, 1-methyl-4- [ 3-methyl-2- [ [ 2-methyl-4- (3, 4, 5-trimethylpyrazol-1-yl) phenoxy ] methyl ] phenyl ] tetrazol-5-one, aminopyrifen, flumetsulam, indazole sulfenamide, (Z, 2E) -5- [1- (4-chlorophenyl) pyrazol-3-yl ] oxy-2-methoxyimino-N, 3-dimethyl-pent-3-enamine, picolinamide (florylpicoxamid), topiramate (fenpicoxamid), iso Ding Yiyang quinoline, isofluorobenzenequinoline (ipflufenoquin), Quinthiram (quinofumelin), ipratropium, N- [2- [2, 4-dichloro-phenoxy ] phenyl ] -3- (difluoromethyl) -1-methyl-pyrazole-4-carboxamide, N- [2- [ 2-chloro-4- (trifluoromethyl) phenoxy ] phenyl ] -3- (difluoromethyl) -1-methyl-pyrazole-4-carboxamide, benthiavalicarb-isopropyl, myclobutanil, 5-amino-1, 3, 4-thiadiazole-2-thiol zinc salt (2:1), fluopyram, fluorothiazolecarbonitrile, fluoroether mycoamide, pyrapropoyne, penconazole (picarbutrazox), fluxapyroxad, 2- (difluoromethyl) -N- (3-ethyl-1, 1-dimethyl-indan-4-yl) pyridine-3-carboxamide, 2- (difluoromethyl) -N- ((3R) -1, 3-trimethylindan-4-yl) pyridine-3-carboxamide, 4- [ [6- [2- (2, 4-difluorophenyl) -1, 1-difluoro-2-hydroxy-3- (1, 2, 4-triazol-1-yl) propyl ] -3-pyridinyl ] oxy ] benzonitrile, metyltetraprole, 2- (difluoromethyl) -N- ((3R) -1, 3-trimethyl-indan-4-yl) pyridine-3-carboxamide, Alpha- (1, 1-dimethylethyl) -alpha- [4'- (trifluoromethoxy) [1,1' -biphenyl ] -4-yl ] -5-pyrimidinecarbonol, trifloxystrobin, enesulfonyl, 4- [ [6- [2- (2, 4-difluorophenyl) -1, 1-difluoro-2-hydroxy-3- (1, 2, 4-triazol-1-yl) propyl ] -3-pyridinyl ] oxy ] benzonitrile, 4- [ [6- [2- (2, 4-difluorophenyl) -1, 1-difluoro-2-hydroxy-3- (5-sulfanyl-1, 2, 4-triazol-1-yl) propyl ] -3-pyridinyl ] oxy ] benzonitrile, trinexade, coumoxystrobin, Zhongshengmycin, thiabendazole, zinc thiazole, amectotractin, iprodione, octylmycoamine, N ' - [ 5-bromo-2-methyl-6- [ (1S) -1-methyl-2-propoxy-ethoxy ] -3-pyridinyl ] -N-ethyl-N-methyl-formamidine, N ' - [ 5-bromo-2-methyl-6- [ (1R) -1-methyl-2-propoxy-ethoxy ] -3-pyridinyl ] -N-ethyl-N-methyl-formamidine, N ' - [ 5-bromo-2-methyl-6- (1-methyl-2-propoxy-ethoxy) -3-pyridinyl ] -N-ethyl-N-methyl-formamidine, N' - [ 5-chloro-2-methyl-6- (1-methyl-2-propoxy-ethoxy) -3-pyridinyl ] -N-ethyl-N-methyl-formamidine, N ' - [ 5-bromo-2-methyl-6- (1-methyl-2-propoxy-ethoxy) -3-pyridinyl ] -N-isopropyl-N-methyl-formamidine (these compounds may be prepared by the methods described in WO 2015/155075), N ' - [ 5-bromo-2-methyl-6- (2-propoxy) -3-pyridinyl ] -N-ethyl-N-methyl-formamidine (this compound may be prepared by the methods described in IPCOM 000249876D), N-isopropyl-N ' - [ 5-methoxy-2-methyl-4- (2, 2-trifluoro-1-hydroxy-1-phenyl-ethyl) phenyl ] -N-methyl-formamidine, N ' - [4- (1-cyclopropyl-2, 2-trifluoro-1-hydroxy-ethyl) -5-methoxy-2-methyl-phenyl ] -N-isopropyl-N-methyl-formamidine (these compounds may be prepared by the methods described in WO 2018/228896), N-ethyl-N ' - [ 5-methoxy-2-methyl-4- [ (2-trifluoromethyl) oxetan-2-yl ] phenyl ] -N-methyl-formamidine, N-ethyl-N ' - [ 5-methoxy-2-methyl-4- [ (2-trifluoromethyl) tetrahydrofuran-2-yl ] phenyl ] -N-methyl-formamidine (these compounds may be prepared by the methods described in WO 2019/110427), N- [ (1R) -1-benzyl-3-chloro-1-methyl-but-3-enyl ] -8-fluoro-quinoline-3-carboxamide, N- [ (1S) -1-benzyl-3-chloro-1-methyl-but-3-enyl ] -8-fluoro-quinoline-3-carboxamide, N- [ (1R) -1-benzyl-3, 3-trifluoro-1-methyl-propyl ] -8-fluoro-quinoline-3-carboxamide, N- [ (1S) -1-benzyl-3, 3-trifluoro-1-methyl-propyl ] -8-fluoro-quinoline-3-carboxamide, N- [ (1R) -1-benzyl-1, 3-dimethyl-butyl ] -7, 8-difluoro-quinoline-3-carboxamide, N- [ (1S) -1-benzyl-1, 3-dimethyl-butyl ] -7, 8-difluoro-quinoline-3-carboxamide, 8-fluoro-N- [ (1R) -1- [ (3-fluorophenyl) methyl ] -1, 3-dimethyl-butyl ] quinoline-3-carboxamide, 8-fluoro-N- [ (1S) -1- [ (3-fluorophenyl) methyl ] -1, 3-dimethyl-butyl ] quinoline-3-carboxamide, N- [ (1R) -1-benzyl-1, 3-dimethyl-butyl ] -8-fluoro-quinoline-3-carboxamide, N- [ (1S) -1-benzyl-1, 3-dimethyl-butyl ] -8-fluoro-quinoline-3-carboxamide, N- ((1R) -1-benzyl-3-chloro-1-methyl-but-3-enyl) -8-fluoro-quinoline-3-carboxamide, n- ((1S) -1-benzyl-3-chloro-1-methyl-but-3-enyl) -8-fluoro-quinoline-3-carboxamide (these compounds may be prepared by the methods described in WO 2017/153380); 1- (6, 7-dimethylpyrazolo [1,5-a ] pyridin-3-yl) -4, 5-trifluoro-3, 3-dimethyl-isoquinoline, 1- (6, 7-dimethylpyrazolo [1,5-a ] pyridin-3-yl) -4, 6-trifluoro-3, 3-dimethyl-isoquinoline, 4-difluoro-3, 3-dimethyl-1- (6-methylpyrazolo [1,5-a ] pyridin-3-yl) isoquinoline, 4, 4-difluoro-3, 3-dimethyl-1- (7-methylpyrazolo [1,5-a ] pyridin-3-yl) isoquinoline, 1- (6-chloro-7-methyl-pyrazolo [1,5-a ] pyridin-3-yl) -4, 4-difluoro-3, 3-dimethyl-isoquinoline (these compounds may be prepared by the methods described in WO 2017/025510); 1- (4, 5-dimethylbenzimidazol-1-yl) -4, 5-trifluoro-3, 3-dimethyl-isoquinoline, 1- (4, 5-dimethylbenzimidazol-1-yl) -4, 4-difluoro-3, 3-dimethyl-isoquinoline, 6-chloro-4, 4-difluoro-3, 3-dimethyl-1- (4-methylbenzimidazol-1-yl) isoquinoline, 4-difluoro-1- (5-fluoro-4-methyl-benzoimidazol-1-yl) -3, 3-dimethyl-isoquinoline, 3- (4, 4-difluoro-3, 3-dimethyl-1-isoquinolinyl) -7, 8-dihydro-6H-cyclopenta [ e ] benzimidazole (these compounds may be prepared by the methods described in WO 2016/156085); N-methoxy-N- [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] cyclopropanecarboxamide, N, 2-dimethoxy-N- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] propionamide, N-ethyl-2-methyl-N- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] propionamide, 1-methoxy-3-methyl-1- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] urea, 1, 3-dimethoxy-1- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] urea, 3-ethyl-1-methoxy-1- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] urea, N- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] propionamide, 4-dimethyl-2- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] isoxazolidin-3-one, 5-dimethyl-2- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] isoxazolidin-3-one, 1- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] pyrazole-4-carboxylic acid ethyl ester, N-dimethyl-1- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] -1,2, 4-triazol-3-amine (these compounds may be prepared from WO 2017/0573 ], WO 2017/055469, WO 2017/093348 and WO 2017/118689, 2- [6- (4-chlorophenoxy) -2- (trifluoromethyl) -3-pyridinyl ] -1- (1, 2, 4-triazol-1-yl) propan-2-ol (which may be prepared by the method described in WO 2017/029179), 2- [6- (4-bromophenoxy) -2- (trifluoromethyl) -3-pyridinyl ] -1- (1, 2, 4-triazol-1-yl) propan-2-ol (which may be prepared by the method described in WO 2017/029179), 3- [2- (1-chlorocyclopropyl) -3- (2-fluorophenyl) -2-hydroxy-propyl ] imidazole-4-carbonitrile (which may be prepared by the method described in WO 2016/156290), 3- [2- (1-chlorocyclopropyl) -3- (3-chloro-2-fluoro-phenyl) -2-hydroxy-propyl ] imidazole-4-carbonitrile (which may be prepared by the method described in WO 2016/1562016), amino-6-methyl-4-pyridines (which may be prepared by the method described in WO 2017/029179), and 5-methyl-4-phenylpyridine (which may be prepared by the method described in WO 2016/1566-phenylpyridine (which may be prepared by the method described in WO 2016/156290) 1H,5H- [1,4] dithiino [2,3-c:5,6-c' ] bipyrrolidinyl-1, 3,5,7 (2H, 6H) -tetraone (this compound can be prepared by the process described in WO 2011/138281), a process for preparing a compound, N-methyl-4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] thiophenecarboxamide, N-methyl-4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide, (Z, 2E) -5- [1- (2, 4-dichlorophenyl) pyrazol-3-yl ] oxy-2-methoxyimino-N, 3-dimethyl-pent-3-enamide (this compound can be prepared by the method described in WO 2018/153707), N '- (2-chloro-5-methyl-4-phenoxy-phenyl) -N-ethyl-N-methyl-formamidine, N' - [ 2-chloro-4- (2-fluorophenoxy) -5-methyl-phenyl ] -N-ethyl-N-methyl-formamidine (this compound can be prepared by the method described in WO 2016/202742), 2- (difluoromethyl) -N- [ (3S) -3-ethyl-1, 1-dimethyl-indan-3-yl ] pyridin-3-carboxamide (this compound can be prepared by the method described in WO 2018/153707), N '- (2-chloro-5-methyl-4-phenoxy-phenyl) -N-ethyl-methyl-formamidine, N' - [ 2-chloro-4- (2-fluorophenoxy) -5-methyl-phenyl ] -N-ethyl-methyl-formamidine (this compound can be prepared by the method described in WO 2016/202742), 2- (difluoromethyl) -N- [ (3S) -3-ethyl-indan-yl-naphth-carboxamide (, (3-methylisoxazol-5-yl) - [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methanone (these compounds may be prepared by the methods described in WO 2017/220485), 2-oxo-N-propyl-2- [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] acetamide (this compound may be prepared by the methods described in WO 2018/065414), ethyl 1- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] -2-thienyl ] methyl ] pyrazole-4-carboxylate (this compound may be prepared by the methods described in WO 2018/158365), 2-difluoro-N-methyl-2- [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] acetamide, n- [ (E) -methoxyiminomethyl ] -4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide, N- [ (Z) -methoxyiminomethyl ] -4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide, N- [ N-methoxy-C-methyl-carboiminol ] -4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide (these compounds can be prepared by the methods described in WO 2018/202428), fluoxastrobin, enesulfonate, trinitropin, coumoxystrobin, N-methoxy-N- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] cyclopropane-carboxamide, N, 2-dimethoxy-N- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] propionamide, N-ethyl-2-methyl-N- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] propionamide, 1-methoxy-3-methyl-1- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] urea, 1, 3-dimethoxy-1- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] urea, 3-ethyl-1-methoxy-1- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] urea, N- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] propionamide, 4-dimethyl-2- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] isoxazolidin-3-one, 5-dimethyl-2- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] isoxazolidin-3-one, 1- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] pyrazole-4-carboxylic acid ethyl ester, N-dimethyl-1- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] -1,2, 4-triazol-3-amine. the compounds in this paragraph can be prepared by the methods described in WO 2017/055473, WO 2017/055469, WO 2017/093348 and WO 2017/118689, 2- [6- (4-chlorophenoxy) -2- (trifluoromethyl) -3-pyridinyl ] -1- (1, 2, 4-triazol-1-yl) propan-2-ol (this compound can be prepared by the methods described in WO 2017/029179), 2- [6- (4-bromophenoxy) -2- (trifluoromethyl) -3-pyridinyl ] -1- (1, 2, 4-triazol-1-yl) propan-2-ol (this compound can be prepared by the methods described in WO 2017/029179), 3- [2- (1-chlorocyclopropyl) -3- (2-fluorophenyl) -2-hydroxy-propyl ] imidazole-4-carbonitrile (this compound may be prepared by the method described in WO 2016/156290), 3- [2- (1-chlorocyclopropyl) -3- (3-chloro-2-fluoro-phenyl) -2-hydroxy-propyl ] imidazole-4-carbonitrile (this compound may be prepared by the method described in WO 2016/156290), 4-phenoxyphenyl) methyl 2-amino-6-methyl-pyridine-3-carboxylate (this compound may be prepared by the method described in WO 2014/006945), 2, 6-dimethyl-1H, 5H- [1,4] dithiino [2,3-c:5,6-c' ] bipyrrolidinyl-1, 3,5,7 (2H, 6H) -tetraon (this compound can be prepared by the method described in WO 2011/138281), N-methyl-4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] thiophenecarboxamide, N-methyl-4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide, (Z, 2E) -5- [1- (2, 4-dichlorophenyl) pyrazol-3-yl ] oxy-2-methoxyimino-N, 3-dimethyl-pent-3-enamide (this compound can be prepared by the method described in WO 2018/153707), N '- (2-chloro-5-methyl-4-phenoxy-phenyl) -N-ethyl-N-methyl-formamidine, N' - [ 2-chloro-4- (2-fluorophenoxy) -5-methyl-phenyl ] -N-ethyl-N-methyl-formamidine (this compound may be prepared by the method described in WO 2016/202742), 2- (difluoromethyl) -N- [ (3S) -3-ethyl-1, 1-dimethyl-indan-4-yl ] pyridine-3-carboxamide (this compound may be prepared by the method described in WO 2014/095675), mesogen, copper thiabendazole, zinc thiazole, amectotractin, Iprodione, cyclo Ding Fujun amine, fluorophenylamine, fluorobenzeneadenine, N- [ (1R) -1-benzyl-3-chloro-1-methyl-but-3-enyl ] -8-fluoro-quinoline-3-carboxamide, N- [ (1S) -1-benzyl-3-chloro-1-methyl-but-3-enyl ] -8-fluoro-quinoline-3-carboxamide, N- [ (1R) -1-benzyl-3, 3-trifluoro-1-methyl-propyl ] -8-fluoro-quinoline-3-carboxamide, N- [ (1S) -1-benzyl-3, 3-trifluoro-1-methyl-propyl ] -8-fluoro-quinoline-3-carboxamide, N- [ (1R) -1-benzyl-1, 3-dimethyl-butyl ] -7, 8-difluoro-quinoline-3-carboxamide, N- [ (1S) -1-benzyl-1, 3-dimethyl-butyl ] -7, 8-difluoro-quinoline-3-carboxamide, 8-fluoro-N- [ (1R) -1- [ (3-fluorophenyl) methyl ] -1, 3-dimethyl-butyl ] quinoline-3-carboxamide, 8-fluoro-N- [ (1S) -1- [ (3-fluorophenyl) methyl ] -1, 3-dimethyl-butyl ] quinoline-3-carboxamide, N- [ (1R) -1-benzyl-1, 3-dimethyl-butyl ] -8-fluoro-quinoline-3-carboxamide, N- [ (1S) -1-benzyl-1, 3-dimethyl-butyl ] -8-fluoro-quinoline-3-carboxamide, N- ((1R) -1-benzyl-3-chloro-1-methyl-but-3-enyl) -8-fluoro-quinoline-3-carboxamide, N- ((1S) -1-benzyl-3-chloro-1-methyl-but-3-enyl) -8-fluoro-quinoline-3-carboxamide, (these compounds may be prepared by the methods described in WO 2017/153380), 1- (6, 7-dimethylpyrazolo [1,5-a ] pyridin-3-yl) -4, 5-trifluoro-3, 3-dimethyl-isoquinoline, 1- (6, 7-dimethylpyrazolo [1,5-a ] pyridin-3-yl) -4, 6-trifluoro-3, 3-dimethyl-isoquinoline, 4, 4-difluoro-3, 3-dimethyl-1- (6-methylpyrazolo [1,5-a ] pyridin-3-yl) isoquinoline, 4-difluoro-3, 3-dimethyl-1- (7-methylpyrazolo [1,5-a ] pyridin-3-yl) isoquinoline, 1- (6-chloro-7-methyl-pyrazolo [1,5-a ] pyridin-3-yl) -4, 4-difluoro-3, 3-dimethyl-isoquinoline (these compounds may be prepared by the methods described in WO 2017/025510), 1- (4, 5-dimethylimidazol-1-yl) -4, 5-trifluoro-3, 3-dimethyl-isoquinoline, 1- (4, 5-Di-benzoimidazol-1-yl) -4, 4-difluoro-3, 3-dimethyl-isoquinoline, 6-chloro-4, 4-difluoro-3, 3-dimethyl-1- (4-methylbenzimidazol-1-yl) isoquinoline, 4-difluoro-1- (5-fluoro-4-methyl-benzoimidazol-1-yl) -3, 3-dimethyl-isoquinoline, 3- (4, 4-difluoro-3, 3-dimethyl-1-isoquinolyl) -7, 8-dihydro-6H cyclopenta [ e ] benzimidazole (these compounds may be prepared by the methods described in WO 2016/156085), N' - [ 5-bromo-2-methyl-6- [ (1S) -1-methyl-2-propoxy-ethoxy ] -3-pyridinyl ] -N-ethyl-N-methyl-formamidine, N ' - [ 5-bromo-2-methyl-6- [ (1R) -1-methyl-2-propoxy-ethoxy ] -3-pyridinyl ] -N-ethyl-N-methyl-carboxamidine, N ' - [ 5-bromo-2-methyl-6- (1-methyl-2-propoxy-ethoxy) -3-pyridinyl ] -N-ethyl-N-methyl-carboxamidine, N ' - [ 5-chloro-2-methyl-6- (1-methyl-2-propoxy-ethoxy) -3-pyridinyl ] -N-ethyl-N-methyl-carboxamidine, N ' - [ 5-bromo-2-methyl-6- (1-methyl-2-propoxy-ethoxy) -3-pyridinyl ] -N-isopropyl-N-methyl-formamidine (these compounds may be prepared by the methods described in WO 2015/155075), N ' - [ 5-bromo-2-methyl-6- (2-propoxy) -3-pyridinyl ] -N-ethyl-N-methyl-formamidine (this compound may be prepared by the methods described in IPCOM 000249876D), N-isopropyl-N ' - [ 5-methoxy-2-methyl-4- (2, 2-trifluoro-1-hydroxy-1-phenyl-ethyl) phenyl ] -N-methyl-formamidine, N ' - [4- (1-cyclopropyl-2, 2-trifluoro-1-hydroxy-ethyl) -5-methoxy-2-methyl-phenyl ] -N-isopropyl-N-methyl-formamidine (these compounds may be prepared by the methods described in WO 2018/228896), N-ethyl-N ' - [ 5-methoxy-2-methyl-4- [ (2-trifluoromethyl) oxetan-2-yl ] phenyl ] -N-methyl-formamidine, N-ethyl-N ' - [ 5-methoxy-2-methyl-4- [ (2-trifluoromethyl) tetrahydrofuran-2-yl ] phenyl ] -N-methyl-formamidine (these compounds may be prepared by the methods described in WO 2019/110427), (5-methyl-2-pyridinyl) - [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methanone, (3-methylisoxazol-5-yl) - [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methanone (these compounds may be prepared by the methods described in WO 2017/220485), 2-oxo-N-propyl-2- [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] acetamide (this compound may be prepared by the methods described in WO 2018/065414), ethyl 1- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] -2-thienyl ] methyl ] pyrazole-4-carboxylate (this compound may be prepared by the methods described in WO 2018/158365), 2-difluoro-N-methyl-2- [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] acetamide, n- [ (E) -methoxyiminomethyl ] -4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide, N- [ (Z) -methoxyiminomethyl ] -4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide, N- [ N-methoxy-C-methyl-carbo-iminol ] -4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide (these compounds can be prepared by the processes described in WO 2018/202428), N- (2-fluorophenyl) -4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide, (2S) -2- [ (4-methoxy-3-propionyloxy-pyridine-2-carbonyl) amino ] propionic acid [ (1S, 2S) -1-methyl-2- (o-tolyl) propyl ] ester, octenimine, chloroindole hydrazide, fluoxastrobin, fluopicolide.

The following mixtures of compounds of formula (I) with active ingredients are preferred (wherein the abbreviation "TX" means "one compound selected from the group consisting of tables a-1 to a-17 and sub-tables thereof and compounds 1.1 to 1.5 defined in table T1"): a compound selected from the group consisting of petroleum +tx, 1-bis (4-chlorophenyl) -2-ethoxyethanol +tx, 2, 4-dichlorophenyl benzenesulfonate +tx, 2-fluoro-N-methyl-N-1-naphthamide +tx, 4-chlorophenyl phenyl sulfone +tx, acetylfipronil +tx, aldicarb +tx, thiotepa +tx, dial-p (amidothioate) +tx, amine phosphorus absorption +TX, hydrogen amine oxalate phosphorus absorption +TX, amitraz +TX, acaricide +TX, arsenic trioxide +TX, azobenzene +TX, azophosphorus +TX, benomyl +TX, benzene Sha Lin (benoxafos) +TX, benzyl benzoate +TX, bixafen +TX, pyrimethanil-TX deltamethrin + TX, brix-thiophos + TX Bromodifen+TX, buprofezin+TX, buketocarb+TX butanone sulfone, butyl pyridaben, lime sulfur (calcium polysulfide) +TX, toxafen, tx, clofenamic, tx, carbothion+TX, cycloimidazole+TX, fenpyroximate+TX, acaricidal (chlorbenside) +TX, insecticidal amidine+TX, insecticidal amidine hydrochloride+TX, acaricidal alcohol+TX, acaricidal ester (chlorfenson) +TX, dimite (chlorfensulfide) +TX, ethylacaricidal alcohol (chlorobenzilate) +TX, itomin (chloromebuform) +TX, chlorfenapyr (chloromethiuron) +TX, propyl ester acaricidal alcohol (chloropropylate) +TX, Fenphos (chlorthiophos) +TX, guathrin (cinerin) I+TX, guathrin II+TX, guathrin (cinerins) +TX, chlorocyanoiodosal (closantel) +TX, coumaphos (coumaphos) +TX, clomiphos (crotamiton) +TX, coumaphos (crotoxyphos) +TX, thiazalin+TX, carprofen (cyanthoate) +TX, DCPM+TX, DDT+TX, trifluophos (demephion) +TX, In the preparation method, the composition comprises the following components of (1) tianlophate-O+TX, tianlophate-S+TX, methyl endophosphate+TX, endophosphate-O+TX, methyl endophosphate-O+TX, endophosphate-S+TX, methyl endophosphate-S+TX, sulfenphos (demeton-S-methylsulfon) +TX, dichlorvos+TX, dicarboxyphenyl (dicyclophos) +TX, benomyl+TX, meflophos (dimefox) +TX, mesifen (dinex) +TX, mesifen (dinex-diclexine) +TX, dichlorvos (dinocap) -4+TX, Dimite Pr-6+TX, dinitrate+TX, nitropentyl (dinopenton) +TX, nitrooctyl (dinosulfon) +TX, nitrobutyl (dinoterbon) +TX, diphos+TX, diphenylsulfone+TX, disulfiram+TX, DNOC+TX, phenoxymite (dofenapyn) +TX, doramectin (doramectin) +TX, genophos (endothion) +TX, eplerin (eprinomectin) +TX, yithion (ethoate-methyl) +TX, Bupirimate (etrimfos) +TX, fenpyrad (fenazaflor) +TX, fenbutatin oxide (fenbutatin oxide) +TX, benfuracarb (fenothiocarb) +TX, fenpyrad+TX, fenpyroximate (fenpyroximate) +TX, fenpyrad (fenpyrazamine) +TX, fenpyroximate (fenson) +TX, flunifedipine (fentrifanil) +TX, fenpyrad (flubenzimine) +TX, flucycloxuron+TX, bifenax (fluenetil) +TX, flufenacet (fluorbenside) +TX, FMC 1137+TX, valicarb+TX, valicarb hydrochloride+TX, carboxin (formparanate) +TX, gamma-HCH+TX, levator+TX, benflumetofen+TX cetyl cyclopropane carboxylate+TX, aqueous amine thiophosphoryl+TX jasmine I+TX, jasmine II+TX jasmine I+TX jasmine pyrethrin II+TX, Acarb + TX, bromomethane + TX, methomyl + TX, carbofuran + TX, milbexime + TX, propylamine fluoro + TX, monocrotophos + TX, locarban + TX, moxidectin + TX, dibromophosphorus (naled) +tx, 4-chloro-2- (2-chloro-2-methyl-propyl) -5- [ (6-iodo-3-pyridinyl) methoxy ] pyridazin-3-one + TX, flumetsulam + TX, nikkomycin + TX, pentacyanocarb 1:1 zinc chloride complex + TX, omethoate + TX, phosphorous sulfinate + TX, phorate + TX, pp' -DDT + TX, parathion + TX, Permethrin+tx, fenphos+tx, vophos+tx, thiocyclophosphorus+tx, phospham+tx, chlorinated turpentine (polychloroterpenes) +tx, acaricide (polynactins) +tx, prochloraz+tx, tick-and-lice+tx, propoxur+tx, ethionamide+TX, lyophobia+TX, pyrethrin I+TX, pyrethrin II+TX, pyrethrin+TX, pyridazinethion+TX, azophoska+TX, quetiapine (quinalphos) +TX, quetiapine (quintiofos) +TX, R-1492+TX, glycifos+TX, rotenone+TX, octamethylphos+TX, captan+TX selametin+TX, su Liu phosphorus+TX, SSI-121+TX selametin+TX, su Liu phosphorus+TX SSI-121+TX tertbutyl-carb+TX, tetraclomite-killing sulfone+TX, acaricidal effect+TX thiafenox+TX, indoxacarb+TX, monocyclocarb+TX methyl ethyl phosphate + TX, g-mite + TX, suiomycin + TX, weijun phosphate + TX, fenbufen + TX, triazophos + TX, Aphis-azalide (triazuron) +TX, triclopyr+TX, trioxypyr+TX Aphiduron+TX, tolfenpyrad (vaniliprole) +TX baishacine (bethoxazin) +TX, copper dioctanoate+TX, copper sulfate+TX, cybutryne+TX, dichloro naphthoquinone+TX dichlorophenol + TX, chlorphenamine + TX, triphenyltin + TX slaked lime+TX, metiram+TX, algicidal quinone+TX slaked lime + TX, sodium zineb + TX algicidal quinone+TX, Piperazine+tx, thiophanate+tx, chloral candy+tx, phoxim+tx, pyridin-4-amine+tx, strychnine+tx, 1-hydroxy-1H-pyridin-2-thione+tx, 4- (quinoxalin-2-ylamino) benzenesulfonamide+tx, 8-hydroxyquinoline sulfate+tx, bronitol+tx, copper hydroxide+tx, cresol+tx, pyrithione+tx, doxine+tx, sodium disultone+tx, formaldehyde+tx, mercuric oxide+tx, kasugamycin+tx, kasugamycin hydrochloride hydrate+tx, nickel bis (dimethyldithiocarbamate) TX, trichloromethyl pyridine+tx, Xin Saitong +TX, oligolinic acid+TX, terramycin+TX, potassium hydroxyquinoline sulfate+TX, thiabendazole+TX, streptomycin+TX, streptomycin sesquisulfate+TX, phyllostachys praecox+TX, thimerosal+TX, phaeda gossypii GV+TX, agrobacterium radiobacter+TX, amblyses species (Amblyseius spp.) +TX, apii graveolens NPV+TX, otsetse wing wasp (Anagrus atomus) +TX, aphis brachycarpa (Aphelinus abdominalis) +TX, aphis gossypii parasitic wasp (Aphidius colemani) +TX, aphis gossypii, Aphid eating goiter (Aphidoletes aphidimyza) +TX, alfalfa silver vein moth NPV+TX, bacillus sphaericus (Bacillus sphaericus Neide) +TX, beauveria bassiana (Beauveria brongniartii) +TX, common green lacewing (Chrysoperla carnea) +TX, cryptomeria monteillonitum (Cryptolaemus montrouzieri) +TX, codling moth GV+TX, siberian from jaw cocoon bee (Dacnusa sibirica) +TX, She Yingji Apis cerana (Diglyphus isaea) +TX, apis cerana+TX, apis cerana (Eretmocerus eremicus) +TX, apis cerana (Heterorhabditis bacteriophora) and Apis grandis (H.megdis) +TX, aleurites maculata (Hippodamia convergens) +TX, aleurites citrina parasitic wasp (Leptomastix dactylopii) +TX, apis lygus (Macrolophus caliginosus) +TX, Cabbage looper NPV+TX, huang Kuobing flea beetles (Metaphycus helvolus) +TX, metarhizium anisopliae (Metarhizium anisopliae var. Acridum) +TX, metarhizium anisopliae microsporidianum variant (Metarhizium anisopliae var. Aniopliae) +TX, european pine needle (Neodiprion sertifer) NPV and Red pine needle (N.lecontei) NPV+TX, orius species+TX, Paecilomyces fumosoroseus (Paecilomyces fumosoroseus) +TX, phytoseis zheieieimeris (Phytoseiulus persimilis) +TX, mao Wen nematodes (STEINERNEMA BIBIONIS) +TX, plutella xylostella (STEINERNEMA CARPOCAPSAE) +TX, spodoptera exigua+TX, grignard nematode (STEINERNEMA GLASERI) +TX, burserus exigua (STEINERNEMA RIOBRAVE) +TX, The composition comprises the components of the formula of (i) a nematode (STEINERNEMA RIOBRAVIS) +tx, (STEINERNEMA SCAPTERISCI) +tx, a mole cricket nematode (Steinernema spp.) +tx, a trichogramma spp. + TX, a western blind spider mite (Typhlodromus occidentalis) +tx, verticillium lecanii (Verticillium lecanii) +tx, azoline (apholate) +tx, bis (aziridine) methylaminophosphine sulfide (bisazir) +tx, busulfan+TX, dimetiff (dimatif) +TX, altretamine (hemel) +TX, hexamethylphosphoric (hempa) +TX, methylnasal discharge bar (metepa) +TX, methylthionasal discharge bar (methiotepa) +TX, methylphosphinazine (methyl apholate) +TX, infertility (morzid) +TX, fluvaluron (penfluron) +TX, nasal discharge bar (tepa) +TX, thiohexamethylphosphoric (thiohempa) +TX, thionasal discharge bar+TX, tritamine+TX, urethane acetate imine+TX, (E) -dec-5-en-1-yl ester and (E) -dec-5-en-1-ol+TX, acetic acid (E) -tridec-4-en-1-yl ester+TX, (E) -6-methylhept-2-en-4-ol+TX, acetic acid (E, Z) -tetradeca-4, 10-dien-1-yl ester+TX, acetic acid (Z) -dodeca-7-en-1-yl ester+TX, (Z) -hexadeca-11-enal+TX, acetic acid (Z) -hexadeca-11-en-1-yl ester+TX, acetic acid (Z) -hexadeca-13-en-11-yn-1-yl ester+TX, (Z) -eicos-13-en-10-one+TX, (Z) -tetradec-7-en-1-al +TX, (Z) -tetradec-9-en-1-ol +TX, acetic acid (Z) -tetradec-9-en-1-yl +TX, acetic acid (7E, 9Z) -dodeca-7, 9-dien-1-yl +TX, acetic acid (9Z, 11E) -tetradec-9, 11-dien-1-yl +TX, acetic acid (9Z, 12E) -tetradec-9, 12-dien-1-yl +TX, 14-methyl octadeca-1-en +TX, 4-methyl-non-5-ol and 4-methyl-non-5-one +TX, alpha-multi-tex +TX, silverfish aggregate pheromone +TX, Dodecadienol (codlelure) +TX, available Mongolian (codlemone) +TX, lure (cuelure) +TX, epoxynonadecane+TX, dodeca-8-en-1-yl acetate+TX, dodeca-9-en-1-yl acetate+TX, dodeca-8, 10-dien-1-yl acetate+TX, bark beetle attractant (dominucure) +TX, 4-methyl ethyl octoate+TX, eugenol+TX, southern pine bark beetle aggregate pheromone (front amine) +TX, lure-to-killing alkene mixture (grandlure) +TX, bark beetle attractant (dominu) and bark beetle attractant (dominu bromide), Trap mixture I+TX, trap mixture II+TX, trap mixture III+TX, trap mixture IV+TX, trap (hexalure) +TX, bark beetle dienol (ipsdienol) +TX, small panol (ipsenol) +TX, chafer sex attractant (japoniure) +TX, trimethyldioxa tricyclononane (lineatin) +TX, noctuid attractant (liture) +TX, noctuid sex attractant (looplure) +TX, trap (medlure) +TX, megatomic acid+TX, pest-trapping ether (methyl eugenol) +TX, pest-trapping alkene (muscalure) +TX, octadecyl-2, 13-dien-1-yl acetate+TX, octadecyl-3, 13-dien-1-yl acetate+TX, he Kangbi (orfraure) +TX, rhinocerotis nata aggregate pheromone (orytalure) +TX, felerance (ostane) +TX, thiocyclam (siglure) +TX, sordidin+TX, edible fungus methyl-trapping alcohol (sulcatol) +TX, tetradec-11-en-1-yl acetate+TX, The Mediterranean fruit fly attractant (trimedlure) +TX, the Mediterranean fruit fly attractant A+TX, the Mediterranean fruit fly attractant B ₁ +TX, the Mediterranean fruit fly attractant B ₂ +TX, the Mediterranean fruit fly attractant C+TX, the trunk-call+TX, the 2- (octyl thio) ethanol+TX, the mosquito repellent ketone (butopyronoxyl) +TX, Butoxy (polypropylene glycol) +TX, dibutyl adipate+TX, dibutyl phthalate+TX, dibutyl succinate+TX, mosquito repellent+TX, mosquito repellent (dimethyl carbate) +TX, dimethyl phthalate+TX, ethylhexyl glycol+TX, hexylurea (hexamide) +TX, mequitin (methoquin-butyl) +TX, methyl neodecanoamide (methylneodecanamide) +TX, oxamate (oxamate) +TX, pacifin (picaridin) +TX, 1-dichloro-1-nitroethane+TX, 1-dichloro-2, 2-bis (4-ethylphenyl) ethane+TX, 1, 2-dichloropropane and 1, 3-dichloropropene+TX, 1-bromo-2-chloroethane+TX, 2-trichloro-1- (3, 4-dichlorophenyl) ethyl acetate+TX, 2-ethylsulfinylethylmethylphosphonate 2, 2-dichloroethylene+TX, dimethylcarbamic acid 2- (1, 3-dithiolan-2-yl) phenyl+TX, thiocyanate 2- (2-butoxyethoxy) ethyl+TX, methylcarbamic acid 2- (4, 5-dimethyl-1, 3-dioxolan-2-yl) phenyl+TX, 2- (4-chloro-3, 5-xylyloxy) ethanol +TX, 2-chlorovinyldiethyl phosphate +TX, 2-imidazolidinone +TX, 2-isovalerylindan-1, 3-dione +TX, 2-methyl (prop-2-ynyl) aminophenyl methylcarbamate +TX, 2-thiocyanoethyl laurate +TX, 3-bromo-1-chloroprop-1-ene +TX, 3-methyl-1-phenylpyrazol-5-yl dimethylcarbamate +TX, 4-methyl (prop-2-ynyl) amino-3, 5-xylyl methylcarbamate +TX, 5-dimethyl-3-oxocyclohex-1-enyl ester +TX, 5-dimethyl-carbamate, Alternethidium +TX, acrylonitrile +TX, alternatives +TX, alomycin +TX, carboxin +TX, alpha-ecdysone +TX aluminum phosphide+TX, methomyl+TX, neonicotinoid+TX, ethyl methidathion (athidathion) +TX, picoline phosphorus+TX Bacillus thuringiensis delta-endotoxin +TX, barium hexafluorosilicate +TX, barium polysulfide +TX, fumigating pyrethrin +TX, bayer 22/190+TX, bayer 22408+TX, beta-cyfluthrin +TX, pentacyclobifhrin (bioethanomethrin) +TX, biothrin+TX, bis (2-chloroethyl) ether+TX, borax+TX, bromophenylphosphorus+TX, bromo-DDT+TX, carbofuran+TX, bendiocarb+TX, terfenaphos (butathiofos) +TX, butylphosphorus+TX, calcium arsenate+TX, calcium cyanide+TX, carbon disulfide+TX, carbon tetrachloride+TX, bardan hydrochloride+TX, sirtuin (cevadine) +TX, borneol dan+TX, chlordan+TX, decachloroketone+TX, chloroform+TX, chloropicrin+TX, chlornitrile oxime phosphorus+TX, chlorpyrazole phosphorus (chlorprazophos) +TX, Cis-bifenthrin (cis-resmethrin) +TX, cis-bifenthrin (cismethrin) +TX, fenvalerate (clocythrin) (alias) +TX, copper acetylarsenite+TX, copper arsenate+TX, copper oleate+TX, livestock phosphorus (coumithoate) +TX, cryolite+TX, CS 708+TX, benzonitrile phosphorus+TX, cartap+TX, cyclosulfamethoxazole+TX, acephate+TX, d-tetramethrin+TX, DAEP+TX, dalong+TX, desmethylcarbofuran (decarbofuran) +TX, De-line (diamidafos) +TX, isochlorophosphorus+TX, de-line phosphorus+TX, dichresyl+TX, dicycloprid+TX, dieldrin+TX, 5-methylpyrazol-3-yl diethyl phosphate vinegar+TX, asthma (dior) +TX, tetrafluoro-methrin+TX, dimchip+TX, permethrin+TX, methylparaben+TX, dichlorfly+TX, prochloraz+TX, penta-nitrophenol+TX, delphagoside+TX, benomyl+TX, vegetable phosphorus+TX, thiopyran phosphorus+TX, DSP+TX, ecdysterone+TX, EI 1642+TX, EMPC+TX, EPBP+TX, etahos+TX, ethionine+TX ethyl formate+tx, dibromoethane+tx, dichloroethane+tx ethyl formate+TX, dibromoethane+TX dichloroethane+TX cyhalothrin+TX, fenphos+TX, ethyl-p-thion+TX Flucloburon (flucofuron) +TX, fenbenphos+TX phosphorus arsenic ester (TX), butyl Thiophosphoryl (TX), furofacial (TX), anti-worm chrysanthemum (TX), biguanide octyl salt (TX), biguanide octyl acetate (TX), HHTN+TX, hydrogen cyanide+TX quinolinyl+TX, IPSP+TX HHTN+TX, hydrogen cyanide+TX, quinolinyl+TX, IPSP+TX chlorzophos+TX, carbochlorimum+TX, isoeuclidean agent+TX Is Liu Lin +TX, transplanting agent+TX, isoprothiolane+TX, oxazolphos+TX, juvenile hormone I+TX, juvenile hormone II+TX, juvenile hormone III+TX, chlorovaleric acid+TX, alkeneyne ester+TX, lead arsenate+TX, bromophenyl phosphorus+TX, acetamiprid+TX, chlorantraniliprole+TX, Thiazolidine+TX, m-isopropylphenyl methyl carbamate+TX, magnesium phosphide+TX azide phosphorus +TX, methyl triazuphos +TX, aphis sulfur phosphorus +TX azide phosphorus plus TX, methyl aphidius phosphorus plus TX aphis sulfur phosphorus and TX butene amine phosphorus +TX, methoprene +TX, methothrin +TX, methox D +TX, methyl isothiocyanate +TX, methyl chloroform +TX dichloromethane+TX, oxadiazon+TX, benomyl+TX nepeptidephosphine+TX, naphthalene+TX, NC-170+TX, nicotine+TX, Nicotine sulfate +TX, nitentothiazine +TX, primordial nicotine +TX, O-ethyl thiophosphonate O-5-dichloro-4-iodophenyl ester +TX, O-4-methyl-2-oxo-2H-benzopyran-7-yl thiophosphonate O, O-diethyl ester +TX, O-6-methyl-2-propylpyrimidin-4-yl thiophosphonate O, O-diethyl ester +TX, dithiopyrophosphoric acid O, O, O ', O' -tetrapropyl ester +TX, oleic acid +TX, p-dichlorobenzene +TX, methyl parathion +TX, pentachlorophenol +TX, pentachlorolaurate +TX, pH 60-38+TX, Fenthion+TX, p-chlorthion+TX, phosphine+TX, methyl octyl thion+TX methamidophos + TX, polychlorinated dicyclopentadiene isomer + TX methamidophos+TX polychlorinated dicyclopentadiene isomer +TX bifenthrin+TX, methomyl+TX, propylthiotepa+TX, pirfenphos+TX antichloraz-Tx+Simarouba extract (quassia) +Tx reverse vermin-killing chrysanthemum (TX) quassia extract (quassia) +TX, ryanodine+TX, rimexodine+TX, sabatroban (sabadilla) +TX, octamethylphos+TX, captan+TX, SI-0009+TX, bupropion+TX, sodium arsenite+TX, sodium cyanide+TX, sodium fluoride+TX, sodium hexafluorosilicate+TX, sodium pentachlorophenate+TX, sodium selenate+TX, sodium thiocyanate+TX, sulfometuron (sulcofuron) +TX, sulfometuron sodium salt (sulcofuron-sodium) +TX, sulfuryl fluoride+TX, thioprop+TX, tar+TX, thiodicarb+TX, TDE+TX, Butyl pyrimidine phosphorus +TX, dithiophosphorus +TX, cyclopen-thrin +TX, tetrachloroethane +TX, thiacloprid +TX, thiocyclam +TX insecticidal oxalate+TX, insecticidal phosphorus+TX, insecticidal single+TX monosultap+TX, tetrabromothrin+TX permethrin+TX, triazamate+TX, coumaphos-3+TX toxic soil phosphine+TX, mixed carbofuran+TX, trifluomethomyl (tolprocarb) +TX toxic soil phosphine plus TX, mixed pesticide plus TX Trifluoromethoxycarb (tolprocarb) +TX, Tolfenpyrad+tx, halothrin+tx, tetrafluorotetramethrin+tx, bis (tributyltin) oxide+tx, bromoacetamide+tx, ferric phosphate+tx, niclosamide-ethanolamine+tx, tributyltin oxide+tx, pyrimorph+tx, snail+tx, 1, 2-dibromo-3-chloropropane+tx, 1, 3-dichloropropene+tx, 3, 4-dichlorotetrahydrothiophene 1, 1-dioxide+tx, 3- (4-chlorophenyl) -5-methyl-rhodanine+tx, 5-methyl-6-thio-1, 3, 5-thiadiazin-3-ylacetic acid+tx, 6-isopentenyl aminopurine+tx, Fluobenzene adenine (anisiflupurin) +TX, benzothiaz (benclothiaz) +TX, cytokinin+TX, DCIP+TX, furfurol+TX, isoamidophosphorus (isamidofos) +TX, kinetin+TX, verrucaria verrucosa composition +TX, tetrachlorothiophene+TX, xylenol+TX, zeatin+TX, potassium ethylxanthate+TX, arabinobenzene+TX, arabinobenzene-S-methyl+TX, giant knotweed (Reynoutria sachalinensis) extract +TX, alpha-chlorohydrin+TX, anto+TX, barium carbonate+TX, biroo urea+TX, bromomouse-long+TX bromadiolone+TX, chlororaterone+TX bromadiolone+TX, bromadiolone+TX chloromurine ketone + TX diphacinone+TX, calciferol+TX, flumetsulam+TX, fluoroacetamide+TX Fluorating+TX, fluorating hydrochloride+TX, murray Telin+TX Fluorating dine +TX, fluorating dine hydrochloride +TX rattel+TX, Rodenticide+tx, 2- (2-butoxyethoxy) ethyl piperonate+tx, 5- (1, 3-benzodioxol-5-yl) -3-hexylcyclohex-2-enone+tx, farnesol+tx with nerolidol, synergistic alkynylether+tx, MGK 264+tx/synergistic ether+tx, synergistic aldehyde+tx, synergistic ester (propyl isomer) +tx, s421+tx, synergistic powder+tx, sesamin (sesasmolin) +tx, sulfoxide+tx, anthraquinone+tx, copper naphthenate+tx, copper king+tx, dicyclopentadiene+tx, a process for the preparation of a pharmaceutical composition comprising the same, Clen+tx, zinc naphthenate+tx, ziram+tx, clothes Ma Ning +tx, ribavirin+tx, chloroindole hydrazide (chloroinconazide) +tx, mercuric oxide+tx, thiophanate-methyl+tx, azaconazole+tx, bitertanol+tx, furfuryl azole+tx, cyproconazole+tx, and difenoconazole+TX, diniconazole+TX, epoxiconazole+TX, fenbuconazole+TX fluquinconazole+TX, flusilazole+TX, flutriafol+TX fluquinconazole+TX, flusilazole+TX flutriafol + TX, myclobutanil+TX, paclobutrazol+TX, fenoxanil+TX, penconazole+TX prothioconazole plus TX, pyripyropene oxime (pyrifenox) +TX prothioconazole plus TX pyripyropene oxime (pyrifenox) +TX fluoroether azole+TX, triazolone+TX triflumizole+TX, triticonazole+TX, pyrimidinyl alcohol+TX Chloropyrimidinol + TX, fluorobenzylpyrimidinol + TX, bupirimate (bupirimate) +TX, triclopyr (dimethirimol) +TX, Ethiprole (ethirimol) +TX, dodecorph+TX fenpropidin (fenpropidin) +TX, fenpropimorph+TX, spiroxamine+TX fenpropidin (fenpropidin) +TX, fenpropimorph+TX spiroxamine + TX fenpiclonil+TX, fludioxonil+TX, benalaxyl (benalaxyl) +TX furalaxyl (furalaxyl) +TX, metalaxyl+TX furalaxyl (furalaxyl) +TX metalaxyl+TX, Prochloraz (debacarb) +TX, wheat germ+TX, thiabendazole+TX, ethiprole (chlorzolate) +TX, sclerotinin (dichlozoline) +TX, tolylene (myclozoline) +TX, procymidone (procymidone) +TX, ethephon (vinclozoline) +TX, boscalid (boscalid) +TX, carboxin+TX, furamide+TX, fluoroamide (flutolanil) +TX, methoxam+TX, carboxin+TX, boscalid, Penthiopyrad (penthiopyrad) +TX, thifluzamide+TX, multocida+TX biguanide octylamine, azoxystrobin, kresoxim-methyl, and kresoxim-methyl biguanide octylamine+TX, azoxystrobin+TX dimoxystrobin + TX phenoxymycylamine+TX, trifloxystrobin+TX, orysastrobin+TX picoxystrobin + TX, pyraclostrobin + TX picoxystrobin+TX, pyraclostrobin+TX pyraclostrobin plus TX, zineb+tx, captan+tx the composition comprises zofuralachlor, folpet, tolylfluanid, fenpropargyl, fenpropathrin, fenpyr Bardo mixture +TX, copper oxide +TX, mancozeb +TX, quinolinium +TX, phthalein + TX, kewensan +TX iprobenfos+TX, clomiphos+TX, tolclomiphos+TX dichlormid+TX, benthiavalicarb+TX, benomyl+TX dichlofluanid plus TX benthiavalicarb isopropyl plus TX, Cyanopyraclostrobin (diclocymet) +TX, pyridaben (dicyclomazine) +TX, chloronitramine (dicloran) +TX, diethofencarb (diethofencarb) +TX, dimethomorph+TX, flumorph+TX, dithianon (dithianon) +TX, ethaboxam (ethaboxam) +TX, hymexazol (etrilazole) +TX, famoxadone+TX, fenamidone) +TX, fenoxanil (fenoxanil) +TX, azophos (ferimzone) +TX, Fluazinam (fluazinam) + TX, flumetylsulforim + TX, fluopyram (fluopicolide) + TX, fluoxytioconazole + TX, sulbactam (flusulfamide) +TX, fluxapyroxad+ TX, cycloxaprop-m+ TX, fosetyl-aluminum (fosetyl-aluminium) +TX, hymexazol (hymexazol) +TX, propineb+ TX, siemens (cyazofamid) +TX, thiodicarb (methasulfocarb) +TX, Benzoquinone+TX, pencycuron (pencycuron) +TX, phthalide+TX, polyoxin (polyoxins) +TX, propamocarb (propamocarb) +TX, pirfencarb+TX, iodoquinodone (proquinazid) +TX, fluquinlone (pyroquinlon) +TX, nalidixic (pyriofenone) +TX, quinoxyfen+TX, pentachloronitrobenzene+TX, tiadinil+TX, imidazosin (triazoxide) +TX, tricyclazole+TX, oxazine+TX, validamycin+TX, pyrifenone+TX, valin+TX, zoxamide (zoxamide) +TX, mandipropamid (mandipropamid) + TX, flubeneteram +TX, isopyrazam+TX, sedaxane+TX, benzovindiflupyr+TX, fluxapyroxamide+TX, 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (3 ',4',5' -trifluoro-biphenyl-2-yl) -amide+TX, iproflumidin (isoflucypram) +TX, isothiabendamine+TX, dipymetitrone + TX, 6-ethyl-5, 7-dioxo-pyrrolo [4,5] [1,4] dithiazolo [1,2-c ] isothiazole-3-carbonitrile+ TX, 2- (difluoromethyl) -N- [ 3-ethyl-1, 1-dimethyl-indan-4-yl ] pyridine-3-carboxamide+ TX, 4- (2, 6-difluorophenyl) -6-methyl-5-phenyl-pyridazin-3-carbonitrile+ TX, (R) -3- (difluoromethyl) -1-methyl-N- [1, 3-trimethylindan-4-yl ] pyrazole-4-carboxamide+ TX, 4- (2-bromo-4-fluoro-phenyl) -N- (2-chloro-6-fluoro-phenyl) -2, 5-dimethyl-pyrazol-3-amine+ TX, 4- (2-bromo-4-fluorophenyl) -N- (2-chloro-6-fluorophenyl) -1, 3-dimethyl-1H-pyrazol-5-amine + TX, fluindapyr + TX, azoxystrobin (jiaxiangjunzhi) + TX, lvbenmixianan + TX, dichlobentiazox + TX, mandelimbin (mandestrobin) +TX, 3- (4, 4-difluoro-3, 4-dihydro-3, 3-dimethylisoquinolin-1-yl) quinolone +TX, 2- [ 2-fluoro-6- [ (8-fluoro-2-methyl-3-quinolinyl) oxy ] phenyl ] propan-2-ol +TX, Thiapiprazole (oxathiapiprolin) +TX, N- [6- [ [ [ (1-methyltetrazol-5-yl) -phenyl-methylene ] amino ] oxymethyl ] -2-pyridyl ] carbamic acid tert-butyl ester + TX, pyraziflumid + TX, inpyrfluxam + TX, trolprocarb +TX, penoxsulam + TX, ipfentrifluconazole +TX, 2- (difluoromethyl) -N- [ (3R) -3-ethyl-1, 1-dimethyl-indan-4-yl ] pyridine-3-carboxamide +TX, N '- (2, 5-dimethyl-4-phenoxy-phenyl) -N-ethyl-N-methyl-formamidine +TX, N' - [4- (4, 5-dichlorothiazol-2-yl) oxy-2, 5-dimethyl-phenyl ] -N-ethyl-N-methyl-formamidine +TX, [2- [3- [2- [3, 5-bis (difluoromethyl) pyrazol-1-yl ] acetyl ] -4-piperidinyl ] thiazol-4-yl ] -4, 5-dihydroisoxazol-5-yl ] -3-chloro-phenyl ] methanesulfonate +TX, N- [6- [ [ (Z) - [ (1-methyltetrazol-5-yl) -phenyl-methylene ] amino ] oxymethyl ] -2-pyridinyl ] carbamic acid but-3-ynyl +TX, Methyl N- [ [5- [4- (2, 4-dimethylphenyl) triazol-2-yl ] -2-methyl-phenyl ] methyl ] carbamate+TX, 3-chloro-6-methyl-5-phenyl-4- (2, 4, 6-trifluorophenyl) pyridazin+ TX, pyridachlometyl +TX, 3- (difluoromethyl) -1-methyl-N- [1, 3-trimethylindan-4-yl ] pyrazole-4-carboxamide+TX, 1- [2- [ [1- (4-chlorophenyl) pyrazol-3-yl ] oxymethyl ] -3-methyl-phenyl ] -4-methyl-tetrazol-5-one+TX, 1-methyl-4- [ 3-methyl-2- [ [ 2-methyl-4- (3, 4, 5-trimethylpyrazol-1-yl) phenoxy ] methyl ] phenyl ] tetrazol-5-one+TX, aminopyrifen + TX, azoxamide+ TX, indazole-sulbactam+ TX, fluxapyroxad+ TX, (Z, 2E) -5- [1- (4-chlorophenyl) pyrazol-3-yl ] oxy-2-methoxyimino-N, 3-dimethyl-pent-3-enamine+ TX, picolinamide (florylpicoxamid) +TX, topiramate (fenpicoxamid) + TX, metarylpicoxamid + TX, iso Ding Yiyang quinoline+ TX, iso-fluorobenzenequinoline (ipflufenoquin) +TX, Quinuprolide (quinofumelin) +TX, ipratropium +TX, 1- [ [4- [ [2- (trifluoromethyl) -1, 3-dioxolan-2-yl ] methoxy ] phenyl ] methyl ] pyrazole-3-carboxylic acid ethyl ester +TX (which can be prepared by the methods described in WO 2020/056090), 1- [ [4- [ (Z) -2-ethoxy-3, 3-trifluoro-prop-1-enoxy ] phenyl ] methyl ] pyrazole-3-carboxylic acid ethyl ester +TX (which can be prepared by the methods described in WO 2020/056090), N- [4- [1- (4-cyclopropyl-2, 6-difluoro-phenyl) pyrazol-4-yl ] -2-methyl-phenyl ] methyl ] carbamic acid methyl ester +TX (which can be prepared by the methods described in WO 2020/097012), Methyl ester of N- [ [4- [1- (2, 6-difluoro-4-isopropyl-phenyl) pyrazol-4-yl ] -2-methyl-phenyl ] methyl ] carbamate+tx (which can be prepared by the method described in WO 2020/097012), 6-chloro-3- (3-cyclopropyl-2-fluoro-phenoxy) -N- [2- (2, 4-dimethylphenyl) -2, 2-difluoro-ethyl ] -5-methyl-pyridazine-4-carboxamide+tx (which can be prepared by the method described in WO 2020/109391), 6-chloro-N- [2- (2-chloro-4-methyl-phenyl) -2, 2-difluoro-ethyl ] -3- (3-cyclopropyl-2-fluoro-phenoxy) -5-methyl-pyridazine-4-carboxamide+tx (which can be prepared by the method described in WO 2020/109391), 6-chloro-3- (3-cyclopropyl-2-fluoro-phenoxy) -N- [2- (3, 4-dimethylphenyl) -2, 2-difluoro-ethyl ] -5-methyl-pyridazine-4-carboxamide +TX (which may be prepared by the method described in WO 2020/109391), N- [2- [2, 4-dichloro-phenoxy ] phenyl ] -3- (difluoromethyl) -1-methyl-pyrazole-4-carboxamide +TX, N- [2- [ 2-chloro-4- (trifluoromethyl) phenoxy ] phenyl ] -3- (difluoromethyl) -1-methyl-pyrazole-4-carboxamide +TX, benzothiostrobin +TX, Fenhexamid+tx, 5-amino-1, 3, 4-thiadiazole-2-thiol zinc salt (2:1) +tx, fluopyram+ TX, flufenoxadiazam +tx, fluothiazolazetidine+tx, fluoroether mycoamide+ TX, pyrapropoyne +tx, piprazole (picarbutrazox) +tx, 2- (difluoromethyl) -N- (3-ethyl-1, 1-dimethyl-indan-4-yl) pyridine-3-carboxamide+tx, 2- (difluoromethyl) -N- ((3R) -1, 3-trimethylindan-4-yl) pyridine-3-carboxamide+tx, 4- [ [6- [2- (2, 4-difluorophenyl) -1, 1-difluoro-2-hydroxy-3- (1, 2, 4-triazol-1-yl) propyl ] -3-pyridinyl ] oxy ] benzonitrile + TX, metyltetraprole +tx, 2- (difluoromethyl) -N- ((3R) -1, 3-trimethylindan-4-yl) pyridine-3-carboxamide +tx, α - (1, 1-dimethylethyl) - α - [4'- (trifluoromethoxy) [1,1' -biphenyl ] -4-yl ] -5-pyrimidinemethanol +tx, trifloxysulf +tx, enoximate +tx, 4- [ [6- [2- (2, 4-difluorophenyl) -1, 1-difluoro-2-hydroxy-3- (1, 2, 4-triazol-1-yl) propyl ] -3-pyridinyl ] oxy ] benzonitrile +tx, 4- [ [6- [2- (2, 4-difluorophenyl) -1, 1-difluoro-2-hydroxy-3- (5-sulfanyl-1, 2, 4-triazol-1-yl) propyl ] -3-pyridinyl ] oxy ] benzonitrile +tx, 4- [6- [2- (2, 4-difluorophenyl) -1, 1-difluoro-2-hydroxy-3- (5-thio-4H-1, 2, 4-triazol-1-yl) propyl ] -3-pyridinyl ] oxy ] benzonitrile +tx, Trinexapac-ethyl + TX, coumoxystrobin + TX, mesogenic + TX, thiabendazole + TX, thiazolium + TX, amectotractin + TX, iprodione + TX, octenimine + TX, N ' - [ 5-bromo-2-methyl-6- [ (1S) -1-methyl-2-propoxy-ethoxy ] -3-pyridinyl ] -N-ethyl-N-methyl-formamidine + TX, N ' - [ 5-bromo-2-methyl-6- [ (1R) -1-methyl-2-propoxy-ethoxy ] -3-pyridinyl ] -N-ethyl-N-methyl-formamidine + TX, N ' - [ 5-bromo-2-methyl-6- (1-methyl-2-propoxy-ethoxy) -3-pyridinyl ] -N-ethyl-N-methyl-formamidine + TX, n' - [ 5-chloro-2-methyl-6- (1-methyl-2-propoxy-ethoxy) -3-pyridinyl ] -N-ethyl-N-methyl-formamidine +TX, N ' - [ 5-bromo-2-methyl-6- (1-methyl-2-propoxy-ethoxy) -3-pyridinyl ] -N-isopropyl-N-methyl-formamidine +TX (these compounds may be prepared by the methods described in WO 2015/155075), N ' - [ 5-bromo-2-methyl-6- (2-propoxy) -3-pyridinyl ] -N-ethyl-N-methyl-formamidine +TX (this compound may be prepared by the methods described in IPCOM 000249876D), N-isopropyl-N ' - [ 5-methoxy-2-methyl-4- (2, 2-trifluoro-1-hydroxy-1-phenyl-ethyl) phenyl ] -N-methyl-formamidine +TX, N ' - [4- (1-cyclopropyl-2, 2-trifluoro-1-hydroxy-ethyl) -5-methoxy-2-methyl-phenyl ] -N-isopropyl-N-methyl-formamidine +TX (these compounds may be prepared by the methods described in WO 2018/228896), N-ethyl-N ' - [ 5-methoxy-2-methyl-4- [ (2-trifluoromethyl) oxetan-2-yl ] phenyl ] -N-methyl-formamidine +TX, N-ethyl-N ' - [ 5-methoxy-2-methyl-4- [ (2-trifluoromethyl) tetrahydrofuran-2-yl ] phenyl ] -N-methyl-formamidine +TX (these compounds may be prepared by the methods described in WO 2019/110427), N- [ (1R) -1-benzyl-3-chloro-1-methyl-but-3-enyl ] -8-fluoro-quinoline-3-carboxamide +TX, N- [ (1S) -1-benzyl-3-chloro-1-methyl-but-3-enyl ] -8-fluoro-quinoline-3-carboxamide +TX, N- [ (1R) -1-benzyl-3, 3-trifluoro-1-methyl-propyl ] -8-fluoro-quinoline-3-carboxamide +TX, N- [ (1S) -1-benzyl-3, 3-trifluoro-1-methyl-propyl ] -8-fluoro-quinoline-3-carboxamide +TX, N- [ (1R) -1-benzyl-1, 3-dimethyl-butyl ] -7, 8-difluoro-quinoline-3-carboxamide +TX, N- [ (1S) -1-benzyl-1, 3-dimethyl-butyl ] -7, 8-difluoro-quinoline-3-carboxamide +TX, 8-fluoro-N- [ (1R) -1- [ (3-fluorophenyl) methyl ] -1, 3-dimethyl-butyl ] quinoline-3-carboxamide +TX, 8-fluoro-N- [ (1S) -1- [ (3-fluorophenyl) methyl ] -1, 3-dimethyl-butyl ] quinoline-3-carboxamide +TX, N- [ (1R) -1-benzyl-1, 3-dimethyl-butyl ] -8-fluoro-quinoline-3-carboxamide +TX, N- [ (1S) -1-benzyl-1, 3-dimethyl-butyl ] -8-fluoro-quinoline-3-carboxamide +TX, N- ((1R) -1-benzyl-3-chloro-1-methyl-but-3-enyl) -8-fluoro-quinoline-3-carboxamide +TX, N- ((1S) -1-benzyl-3-chloro-1-methyl-but-3-enyl) -8-fluoro-quinoline-3-carboxamide +TX (these compounds may be prepared by the methods described in WO 2017/153380), 1- (6, 7-dimethylpyrazolo [1,5-a ] pyridin-3-yl) -4, 5-trifluoro-3, 3-dimethyl-isoquinoline +TX, 1- (6, 7-dimethylpyrazolo [1,5-a ] pyridin-3-yl) -4, 6-trifluoro-3, 3-dimethyl-isoquinoline +TX, 4-difluoro-3, 3-dimethyl-1- (6-methylpyrazolo [1,5-a ] pyridin-3-yl) isoquinoline +TX, 4, 4-difluoro-3, 3-dimethyl-1- (7-methylpyrazolo [1,5-a ] pyridin-3-yl) isoquinoline +TX, 1- (6-chloro-7-methyl-pyrazolo [1,5-a ] pyridin-3-yl) -4, 4-difluoro-3, 3-dimethyl-isoquinoline +TX (these compounds may be prepared by the methods described in WO 2017/025510), 1- (4, 5-dimethylbenzimidazol-1-yl) -4, 5-trifluoro-3, 3-dimethyl-isoquinoline +TX, 1- (4, 5-dimethylbenzimidazol-1-yl) -4, 4-difluoro-3, 3-dimethyl-isoquinoline +TX, 6-chloro-4, 4-difluoro-3, 3-dimethyl-1- (4-methylbenzimidazol-1-yl) isoquinoline +TX, 4-difluoro-1- (5-fluoro-4-methyl-benzoimidazol-1-yl) -3, 3-dimethyl-isoquinoline +TX, 3- (4, 4-difluoro-3, 3-dimethyl-1-isoquinolyl) -7, 8-dihydro-6H-cyclopenta [ e ] benzimidazole +TX (these compounds may be prepared by the methods described in WO 2016/156085); N-methoxy-N- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] cyclopropanecarboxamide +TX ], N, 2-dimethoxy-N- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] propionamide+TX, N-ethyl-2-methyl-N- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] propionamide+TX, 1-methoxy-3-methyl-1- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] urea+TX, 1, 3-dimethoxy-1- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] urea+TX, 3-ethyl-1-methoxy-1- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] urea +tx, N- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] propanamide +tx, 4-dimethyl-2- [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] isoxazolidin-3-one +tx, 5-dimethyl-2- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] isoxazolidin-3-one +tx, 4-dimethyl-2- [ [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] isoxazolidin-3-one +tx, 1- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] pyrazole-4-carboxylic acid ethyl ester +tx, N-dimethyl-1- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] -1,2, 4-triazol-3-amine +tx. the compounds in this paragraph can be obtained from WO 2017/055473, WO 2017/055469, WO 2017/093348 and WO 2017/118689, 2- [6- (4-chlorophenoxy) -2- (trifluoromethyl) -3-pyridinyl ] -1- (1, 2, 4-triazol-1-yl) propan-2-ol+tx (which may be prepared by the method described in WO 2017/029179), 2- [6- (4-bromophenoxy) -2- (trifluoromethyl) -3-pyridinyl ] -1- (1, 2, 4-triazol-1-yl) propan-2-ol+tx (which may be prepared by the method described in WO 2017/029179), 3- [2- (1-chlorocyclopropyl) -3- (2-fluorophenyl) -2-hydroxy-propyl ] imidazole-4-carbonitrile+tx (which may be prepared by the method described in WO/156290), 3- [2- (1-chlorocyclopropyl) -3- (3-fluoro-phenyl) -2-hydroxy-propyl ] imidazole-4-carbonitrile+tx (which may be prepared by the method described in WO 2017/029179), and amino-plastic (which may be prepared by the method of WO 2017/029179) 2, 6-dimethyl-1H, 5H- [1,4] dithiino [2,3-c:5,6-c ' ] bipyrrolidinyl-1, 3,5,7 (2H, 6H) -tetraone +TX (this compound can be prepared by the process described in WO 2011/138281); N-methyl-4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] thiobenzamide +TX, N-methyl-4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide +TX, (Z, 2E) -5- [1- (2, 4-dichlorophenyl) pyrazol-3-yl ] oxy-2-methoxyimino-N, 3-dimethyl-pent-3-enamide +TX (this compound can be prepared by the method described in WO 2018/153707), N ' - (2-chloro-5-methyl-4-phenoxy-phenyl) -N-ethyl-N-methyl-formamidine +TX, N ' - [ 2-chloro-4- (2-fluorophenoxy) -5-methyl-phenyl ] -N-ethyl-N-methyl-formamidine +TX (this compound can be prepared by the method described in WO 2016/742), 2- (difluoromethyl) -N- [ (3S) -3-ethyl-1, 1-202-4-dimethyl-tetralin ] Pyridine-3-carboxamide + TX (this compound can be prepared by the method described in WO 2014/095675), (5-methyl-2-pyridinyl) - [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methanone + TX, (3-methylisoxazol-5-yl) - [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methanone+TX (these compounds may be prepared by the methods described in WO 2017/220485), 2-oxo-N-propyl-2- [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] acetamide+TX (this compound may be prepared by the methods described in WO 2018/065414), 1- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] -2-thienyl ] methyl ] pyrazole-4-carboxylic acid ethyl ester+TX (this compound may be prepared by the methods described in WO 2018/158365), 2-difluoro-N-methyl-2- [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] acetamide+TX, 1- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] acetamide+TX, N- [ (E) -methoxyiminomethyl ] -4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide+tx, N- [ (Z) -methoxyiminomethyl ] -4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide+tx, N- [ N-methoxy-C-methyl-carboimino ] -4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide+tx (these compounds can be prepared by the methods described in WO 2018/202428).

The reference in parentheses after the active ingredient, for example, [3878-19-1], means a chemical abstract registration number. The above described mixed formulations are known. In the case where the active ingredients are included in "THE PESTICIDE Manual [ handbook of pesticides ]" [ THE PESTICIDE Manual-AWorld Compendium [ handbook of pesticides-global overview ]; 13 th edition; editions: C.D.S. TomLin; the British Crop Protection Council [ England crop protection Committee ] ], they are described therein with the entry numbers given in parentheses above for the particular compound, for example, the compound "Abametin" is described with the entry number (1). In the case where "[ CCN ]" is added to a specific compound above, said compound is included in "Compendium of Pesticide Common Names [ pesticide common name schema ]" which can be found in the internet [ a.wood; compendiumofPesticideCommonNames, copy1995-2004], For example, the compound "acetylfipronil" is described in the internet address http:// www.alanwood.net/pesticides/acetoprole.

Most of the above-mentioned active ingredients are mentioned by the so-called "common name" hereinabove, with the relevant "ISO common name" or another "common name" being used in the individual case. In case the name is not a "common name", the name category used is replaced by the name given in parentheses for the specific compound, in which case IUPAC name, IUPAC/chemical abstract name, "chemical name", "conventional name", "compound name" or "development code" is used, or "alias" is used if neither one of those names nor "common name" is used. "CAS registry number" means a chemical abstract registry number.

The active ingredient mixtures of the compounds of the formula (I) (selected from one of the compounds as shown in tables A-1 to A-17 and sub-tables thereof (hereinbelow), or the compounds 1.1 to 1.5 listed in Table T1 (hereinbelow)) are preferably in a mixing ratio of from 100:1 to 1:6000, in particular in a ratio of from 50:1 to 1:50, more in particular in a ratio of from 20:1 to 1:20, even more in particular in a ratio of from 10:1 to 1:10, very in particular in a ratio of from 5:1 and 1:5, particularly preferably in a ratio of from 2:1 to 1:2, and also in a ratio of from 4:1 to 2:1 is preferred, particularly at a ratio of 1:1, or 5:1, or 5:2, or 5:3, or 5:4, or 4:1, or 4:2, or 4:3, or 3:1, or 3:2, or 2:1, or 1:5, or 2:5, or 3:5, or 4:5, or 1:4, or 2:4, or 3:4, or 1:3, or 2:3, or 1:2, or 1:600, or 1:300, or 1:150, or 1:35, or 2:35, or 4:35, or 1:75, or 2:75, or 4:75, or 1:6000, or 1:3000, or 1:1500, or 1:350, or 2:350, or 4:350, or 1:750, or 2:750, or 4:750. Those mixing ratios are by weight.

The mixture as described above may be used in a method of controlling pests, which method comprises administering a composition comprising the mixture as described above to the pest or its environment, except for methods for treating the human or animal body by surgery or therapy and diagnostic methods carried out on the human or animal body.

Mixtures comprising the compounds as shown in tables a-1 to a-17 and sub-tables thereof (below), or the compounds 1.1 to 1.5 listed in table T1 (below), and one or more of the active ingredients as described above, may be administered, for example, in a single "ready-to-use" form, in a combined spray mixture (which consists of separate formulations of the single active ingredient components) (e.g. "tank mix") and when administered in a sequential manner (i.e. one after another for a moderately short period of time, such as hours or days) in combination with these single active ingredients. The order of administration of the compounds as shown in tables A-1 to A-17 and their sub-tables (below), or of the compounds 1.1 to 1.5 listed in Table T1 (below), and of the one or more active ingredients as described above is not critical to the practice of the invention.

The compounds of the invention may also be used in combination with anthelmintic agents. Such anthelmintic agents include compounds selected from the group consisting of macrolides, such as ivermectin, abamectin, emamectin, eprinomectin, doramectin, selamectin, moxidectin, neminomectin and milbemycin derivatives, as described in EP-357460, EP-444964 and EP-594291. Additional anthelmintic agents include semisynthetic and biosynthetic avermectin/milbemycin derivatives, such as those described in US-5015630, WO-9415944 and WO-9522552. Additional anthelmintic agents include benzimidazoles such as albendazole, candidazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxbendazole, pamidazole and other members of this class. Additional anthelmintic agents include imidazothiazoles and tetrahydropyrimidines such as tetraimidazole, levamisole, thiopyrimidine pamoate, octotel or morantel. Additional anthelmintic agents include flukicides (e.g., triclabendazole and closuluron) and tapecides (e.g., praziquantel and exenatide).

The compounds of the present invention may be used in combination with derivatives and analogues of para-herceptin (paraherquamide)/marcfortine (marcfortine) anthelmintic agents, and the antiparasitic agents oxazolines, such as those disclosed in US-5478855, US-4639771 and DE-19520936.

The compounds of the invention may be used in combination with derivatives and analogues of the general class of dioxomorpholinium antiparasitic agents as described in WO 96/15121, and also with helminthic active cyclic depsipeptides such as those described in WO 96/11945, WO 93/19053, WO 93/25543, EP 0 626 375, EP 0 382 173, WO 94/19334, EP 0 382 173 and EP 0 503 538.

The compounds of the invention may be used in combination with other ectoparasiticides (ectoparasiticide), for example fipronil, pyrethroids, organophosphates, insect growth regulators such as lufenuron, ecdysone agonists such as tebufenozide and the like, neonicotinoids such as imidacloprid and the like.

The compounds of the present invention may be used in combination with terpene alkaloids, such as those described in International patent application publication No. WO 95/19363 or WO 04/72086, in particular the compounds disclosed therein.

Other examples of such bioactive compounds that may be used in combination with the compounds of the present invention include, but are not limited to, the following:

Organic phosphate: acephate, methyl piroxicam, ethyl phoxim, methyl phoxim, bromphos, ethyl bromophos, thiophos, tetraphos (chlorethoxyphos), chlorpyrifos, clofenamate, clofos, endophos-S-methyl sulfone, chlorimphos, diazinon, dichlorvos, chlorothalophos, dimethoate, ethahos, ethion, acephate, oxapyrifos, valaphos, benfophos, fenitrothion, pirfenphos, dinotefos, ambofos, fosthiazate, heptenophos, chlorzophos, isoxazophos, malathion, chlorpyrifos fenphos, methamidophos, methidathion, methylparathion, acephate, monocrotophos, dibromophosphorus, omethoate, methyl oxo-endophosphate, paraoxon, parathion, methyl parathion, phenthoate, phoxim, carbophos, iminophos, phosphamidon, phorate, oxime thiophos, pyrimidon-methyl, profenofos, proetamphos, profenofos, pyrazophos, pyridazinethion, quinophos, thiopropos, temephos, terbufos, butyl pyrimidine phosphorus, setrophos, dimethyl thiophos (thimeton), triazophos, trichlorfon, aphos.

Carbamate, carbofuran, aldicarb, 2-sec-butylphenyl methyl carbamate, benfuracarb, carbofuran, carbosulfan, carbofuran, ethiprole, benoxil, fenbucarb, furacarb, HCN-801, isoprocarb, indoxacarb, methomyl, 5-methyl-m-isopropylbutachlor (methyl) carbamate, methomyl, pirimicarb, propoxur, thiodicarb, monocrotophos, triazamate, UC-51717.

Pyrethroid: fluoroallethrin, allyl pyrethrin, cis-cypermethrin, 5-benzyl-3-furanmethyl (E) - (1R) -cis-2, 2-dimethyl-3- (2-oxothiolane-3-ylidenemethyl) cyclopropanecarboxylate, bifenthrin, beta-cyfluthrin, alpha-cyfluthrin, beta-cyfluthrin, bio-propethrin ((S) -cyclopentyl isomer), bio-bifenthrin, NCI-85193, beta-cythrin, lambda-cyhalothrin, beta-cyhalothrin enetetramethrin, fenvalerate, ethofenprox, pencythrin, fenpropathrin, fenvalerate, flumethrin, fluvalinate, cyfluthrin (D isomer), prallethrin, cyfluthrin, lambda-cyhalothrin permethrin, phenothrin, propathrin, pyrethrin (natural product), bifenthrin, tetramethrin, transfluthrin, theta-cypermethrin, flusilathrin, t-cyfluthrin, tefluthrin, tetrabromothrin, zeta-cypermethrin.

Arthropod growth regulator comprising a) chitin synthesis inhibitor comprising chlorantraniliprole, chlorpyrifos, flufenuron, flufenoxuron, hexaflumuron, chlorfenouron, fenuron, chlorfluazuron, chlorpyrifos, buprofezin, fenbucin, fenbuconazole, tebufenozide (chlorfentazine), b) ecdysone antagonist comprising chlorfenozide, methoxyfenozide and tebufenozide, c) juvenile hormone analogue comprising pyriproxyfen, methoprene (including S-methoprene) and fenoxycarb, and d) lipid biosynthesis inhibitor comprising spirodiclofen.

Other antiparasitic agents: the composition comprises chlorfenapyr, amitraz, AKD-1022, ANS-118, azadirachtin, bacillus thuringiensis, monosulfuron, bifenazate, le-miticide, fenisobromolate, BTG-504, BTG-505, toxafen, cartap, fenitrothion, chlorfenapyr, amitraz, clotrimazole, chlorfenapyr, dichlozene (diacloden), chlorfenapyr, DBI-3204, bivolin, dihydroxymethyl dihydroxypyrrolidine, diuron, dimite, difenpropade, thiodane, ethiprole, fenthrin, fenazaquin, flufenzine (flumite), MTI-800, fenpyroximate, azoxystrobin, flufenpyrad, brofenprox, flufenzine, trifluor, benzyl ether (fluproxyfen), benzyl ether (halofenprox) Fluofuzozone, IKI-220, kenali, NC-196, mentha indicum (neem guard), nedinofuran (nidinorterfuran), nitenpyram, SD-35651, WL-108477, pyridalyl, kemite, profenofos (protrifenbute), pymetrozine, pyridaben, pyriminobac-methyl, NC-1111, R-195, RH-0345, RH-2485, RYI-210, S-1283, S-1833, SI-8601, silafluofen, silicon Luo Mating (silomadine), spinosad, tebufenpyrad, trichlorfon, tetramycin, thiacloprid, thiocyclam, tolfenpyrad, triazamate, triazophos, synergistic propargyl, bortezophos (vertalec), YI-5301.

Biological agents include Bacillus thuringiensis Sasa Hua Yachong (Bacillus thuringiensis ssp aizawai), bacillus thuringiensis Coulosa subspecies (kurstaki), bacillus thuringiensis delta endotoxins, baculoviruses, entomopathogenic bacteria, viruses and fungi.

Bactericides, namely aureomycin, terramycin and streptomycin.

Other biological agents include enfluroxacin, febantel, penciclovir, meloxicam, cefalexin, kanamycin, p Mo Ben, clenbuterol, omeprazole, thiomerrill, benazepril, pi Ruipu (pyriprole), cefquinome, florfenicol, buserelin, ceftazidime, tolaccan, ceftiofur, carprofen, meflozonone, praziquantel, triclabendazole.

The compositions according to the invention may also comprise other solid or liquid adjuvants, such as stabilizers, for example non-epoxidized or epoxidized vegetable oils (for example epoxidized coconut oil, rapeseed oil or soybean oil), defoamers (for example silicone oils), preservatives, viscosity regulators, binders and/or adhesion promoters, fertilizers or other active ingredients for achieving a particular effect, for example bactericides, fungicides, nematicides, plant activators, molluscicides or herbicides.

The compositions according to the invention are prepared in a manner known per se, for example by grinding, sieving and/or compacting the solid active ingredient in the absence of auxiliaries, and in the presence of at least one auxiliary, for example by intimately mixing the active ingredient with one or more auxiliaries and/or grinding the active ingredient with one or more auxiliaries. These processes for preparing the compositions and the use of the compounds (I) for preparing these compositions are also subjects of the invention.

Another aspect of the invention relates to the use of a fungicidal or insecticidal mixture having a compound of formula (I) or preferably a separate compound as defined herein, comprising at least one compound of formula (I) or at least one preferred separate compound as defined above, or comprising at least one compound of formula (I) or at least one preferred separate compound as defined above, mixed with other fungicides or insecticides as described above, for controlling or preventing infestation of plants (e.g. useful plants (e.g. crop plants)), propagation material (e.g. seeds) thereof, harvested crops (e.g. harvested grain crops), or non-living material by insects or phytopathogenic microorganisms (preferably fungal organisms).

Another aspect of the invention relates to a method of controlling or preventing infestation of plants, such as useful plants (e.g. crop plants), propagation material thereof (e.g. seeds), harvested crops (e.g. harvested food crops), or non-living material by insects or phytopathogenic or spoilage microorganisms or organisms potentially harmful to humans, especially fungal organisms, which comprises applying a compound of formula (I) or preferably a separate compound as defined above as an active ingredient to the plants, to parts of the plants or to the locus thereof, to propagation material thereof, or to any part of the non-living material.

Control or prevention means reducing infestation or decay by phytopathogenic microorganisms or potentially harmful organisms to humans, especially fungal organisms, to such a level that is proved to be improved.

A preferred method of controlling or preventing infestation of crop plants by phytopathogenic microorganisms, especially fungal organisms, or insects is foliar application, which comprises applying a compound of formula (I), or an agrochemical composition which contains at least one of the compounds. The frequency and rate of application will depend on the risk of infestation by the corresponding pathogen or insect. However, the compounds of formula (I) can also penetrate plants via the soil through the roots (systemic action) by wetting the locus of the plants with a liquid formulation or by applying the compounds in solid form, for example in granular form, to the soil (soil application). In rice crops, such granules may be applied to irrigated paddy fields. The compounds of formula (I) may also be applied to the seeds (coatings) by impregnating the seeds or tubers with a liquid formulation of the fungicide or coating them with a solid formulation.

Formulations, for example compositions containing a compound of formula (I) and, if desired, a solid or liquid adjuvant or monomers for encapsulating a compound of formula (I), can be prepared in a known manner, typically by intimately mixing and/or grinding the compound with extenders, such as solvents, solid carriers and optionally surface-active compounds (surfactants).

The advantageous application rate is generally from 5g to 2kg of active ingredient (a.i.) per hectare (ha), preferably from 10g to 1kg a.i./ha, most preferably from 20g to 600g a.i./ha. When used as a seed soaking agent, a suitable dosage is from 10mg to 1g of active substance per kg of seed.

When the combination according to the invention is used for treating seeds, a ratio of from 0.001 to 50g of compound having formula (I) per kg of seed, preferably from 0.01 to 10g/kg of seed, is generally sufficient.

Suitably, the composition comprising the compound of formula (I) according to the invention is applied prophylactically (meaning before disease development) or healthily (meaning after disease development).

The compositions OF the invention may be used in any conventional form, for example in the form OF a double-pack, dry seed-treating powder (DS), seed-treating Emulsion (ES), seed-treating flowable concentrate (FS), seed-treating solution (LS), seed-treating water-dispersible powder (WS), seed-treating capsule suspension (CF), seed-treating Gel (GF), emulsion Concentrate (EC), suspension Concentrate (SC), suspension Emulsion (SE), capsule Suspension (CS), water-dispersible particles (WG), emulsifiable particles (EG), water-in-oil Emulsion (EO), oil-in-water Emulsion (EW), microemulsion (ME), dispersible oil suspension (OD), oil suspension (OF), oil-soluble concentrate (OL), soluble concentrate (SL), ultra-low volume Suspension (SU), ultra-low volume liquid (UL), master drug (TK), dispersible Concentrate (DC), wettable Powder (WP) or any technically feasible formulation in combination with agriculturally acceptable adjuvants.

Such compositions can be produced in a conventional manner, for example by mixing the active ingredient with suitable formulation inert agents (diluents, solvents, fillers and optionally other formulation ingredients, such as surfactants, biocides, antifreeze agents, adhesion agents, thickeners and compounds providing auxiliary effects). Conventional slow release formulations aimed at long lasting efficacy may also be used. In particular, formulations to be applied in spray form (e.g., water-dispersible concentrates (e.g., EC, SC, DC, OD, SE, EW, EO, etc.), wettable powders, and granules) may contain surfactants (e.g., humectants and dispersants) and other compounds that provide a adjunctive effect, such as condensation products of formaldehyde with naphthalene sulfonates, alkylaryl sulfonates, lignin sulfonates, fatty alkyl sulfates, and ethoxylated alkylphenols and ethoxylated fatty alcohols.

The seed dressing formulations are applied to the seeds in a manner known per se in the form of suitable seed dressing formulations, for example in the form of aqueous suspensions or dry powders which have good adhesion to the seeds, using the combinations and diluents of the invention. Such seed dressing formulations are known in the art. Seed dressing formulations may contain the individual active ingredients or combinations of active ingredients in encapsulated form, for example as slow release capsules or microcapsules.

Typically, these formulations comprise from 0.01 to 90% by weight of an active agent consisting of at least a compound of formula (I), optionally together with other active agents (in particular microbiocides or preservatives etc.), from 0 to 20% of an agriculturally acceptable surfactant and from 10 to 99.99% of a solid or liquid formulation inert agent and one or more adjuvants. The concentrated form of the composition typically contains between about 2% and 80%, preferably between about 5% and 70% by weight of active agent. The formulation may for example contain from 0.01 to 20% by weight, preferably from 0.01 to 5% by weight, of active agent in the form of administration. However, commercial products will preferably be formulated as concentrates and the end user will typically use dilute formulations.

However, it is preferred that the commercial product is formulated as a concentrate and the end user will typically use a diluted formulation.

The compounds according to tables A-1 to A-17 below and the sub-tables hereinbelow can be prepared according to the methods described above. The following examples are intended to illustrate the invention and demonstrate preferred compounds of formula (Ia).

Compounds having formula (Ia) wherein R ¹、R⁷、R⁸, and R ⁹ are defined in tables a-1 to a-17, and G is defined in table Z below:

Table Z

Table A-1 Compounds having the formula (Ia-A-1) wherein R ¹、R⁷、R⁸, and R ⁹ are defined in tables A-1a to A-1k and G is defined in Table Z above:

Table A-1a this sub-table provides 9 compounds A-1a.01 to A-1a.12 of formula (Ia-A-1) wherein R ¹ is 3-cyclopropyl-2-fluorophenyl, R ⁸ and R ⁹ are hydrogen and the substituents G are as defined in Table Z above.

Table A-1b this table provides 9 compounds A-1b.01 and A-1b.12 of formula (Ia-A-1) wherein R ¹ is 3- (trifluoromethyl) phenyl, R ⁸ and R ⁹ are hydrogen and substituent G is a substituent G as defined in Table Z above.

Table A-1c this table provides 9 compounds A-1c.01 and A-1c.12 of formula (Ia-A-1) wherein R ¹ is 3-ethynylphenyl, R ⁸ and R ⁹ are hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-1d this table provides 9 compounds A-1d.01 and A-1d.12 of formula (Ia-A-1) wherein R ¹ is 3-chlorophenyl, R ⁸ and R ⁹ are hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-1e this table provides 9 compounds A-1e.01 and A-1e.12 of formula (Ia-A-1) wherein R ¹ is 5-cyanopyridin-3-yl, R ⁸ and R ⁹ are hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-1f this table provides 9 compounds A-1f.01 and A-1f.12 of formula (Ia-A-1) wherein R ¹ is 3-cyclopropylphenyl, R ⁸ and R ⁹ are hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-1G this table provides 9 compounds of formula (Ia-A-1) A-1g.01 and A-1g.12, where R ¹ is 3-phenyl, R ⁸ and R ⁹ are hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-1h this table provides 9 compounds A-1h.01 and A-1h.12 of formula (Ia-A-1) wherein R ¹ is 3-tolyl, R ⁸ and R ⁹ are hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-1i this table provides 9 compounds A-1i.01 to A-1i.12 of formula (Ia-A-1) wherein R ¹ is 3-cyclopropylphenyl, R ⁸ is methyl and R ⁹ is hydrogen and substituent G is substituent G as defined in Table Z above.

For example, compound A-1i.01 is:

Table A-1j this table provides 9 compounds A-1j.01 and A-1j.12 of formula (Ia-A-1) wherein R ¹ is 3- (trifluoromethyl) phenyl, R ⁸ is chlorine and R ⁹ is hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-1k this table provides 9 compounds A-1k.01 and A-1k.12 of formula (Ia-A-1) wherein R ¹ is 5-cyanopyridin-3-yl, R ⁸ is hydrogen and R ⁹ is chlorine and substituent G is substituent G as defined in Table Z above.

Table A-2 Compounds having the formula (Ia-A-2) wherein R ¹、R⁷、R⁸, and R ⁹ are defined in tables A-2a to A-2i and G is defined in Table Z above:

Table A-2a this table provides 9 compounds A-2a.01 and A-2a.12 of formula (Ia-A-2) wherein R ¹ is 3-cyclopropyl-2-fluorophenyl, R ⁷ and R ⁹ are hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-2b this table provides 9 compounds A-2b.01 and A-2b.12 of formula (Ia-A-2) wherein R ¹ is 3- (trifluoromethyl) phenyl, R ⁷ and R ⁹ are hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-2c this table provides 23 compounds A-2c.01 and A-2c.12 of formula (Ia-A-2) wherein R ¹ is 3-ethynylphenyl, R ⁷ and R ⁹ are hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-2d this table provides 9 compounds A-2d.01 and A-2d.12 of formula (Ia-A-2) wherein R ¹ is 3-chlorophenyl, R ⁷ and R ⁹ are hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-2e this table provides 9 compounds A-2e.01 and A-2e.12 of formula (Ia-A-2) wherein R ¹ is 5-cyanopyridin-3-yl, R ⁷ and R ⁹ are hydrogen and substituent G is substituent G as defined in Table Z above.

For example, compound a-2e.09 is:

table A-2f this table provides 9 compounds of formula (Ia-A-2) A-2g.01 and A-2g.9, where R ¹ is 3-cyclopropylphenyl, R ⁷ and R ⁹ are hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-2G this table provides 9 compounds of formula (Ia-A-2) A-2h.01 and A-2h.9 wherein R ¹ is 3-cyclopropyl-2-fluorophenyl, R ⁷ is hydrogen, R ⁹ is methyl and substituent G is substituent G as defined in Table Z above.

Table A-2h this table provides 9 compounds A-2i.01 and A-2i.9 having the formula (Ia-A-2) wherein R ¹ is 3- (trifluoromethyl) phenyl, R ⁷ is hydrogen, R ⁹ is methyl and substituent G is substituent G as defined in Table Z above.

Table A-2i this table provides 9 compounds A-2j.01 and A-2j.9 of formula (Ia-A-2) wherein R ¹ is 5-cyanopyridin-3-yl, R ⁷ is methyl, R ⁹ is hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-3 Compounds having the formula (Ia-A-3) wherein R ¹、R⁷、R⁸, and R ⁹ are defined in tables A-3a to A-3m and G is defined in Table Z above:

Table A-3a this table provides 9 compounds A-3a.01 and A-3a.12 of formula (Ia-A-3) wherein R ¹ is 3-cyclopropyl-2-fluorophenyl, R ⁷ and R ⁸ are hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-3b this table provides 9 compounds A-3b.01 and A-3b.12 of formula (Ia-A-3) wherein R ¹ is 3- (trifluoromethyl) phenyl, R ⁷ and R ⁸ are hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-3c this table provides 9 compounds A-3c.01 and A-3c.12 of formula (Ia-A-3) wherein R ¹ is 3-ethynylphenyl, R ⁷ and R ⁸ are hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-3d this table provides 9 compounds A-3d.01 and A-3d.12 of formula (Ia-A-3) wherein R ¹ is 3-chlorophenyl, R ⁷ and R ⁸ are hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-3e this table provides 9 compounds A-3e.01 and A-3e.12 of formula (Ia-A-3) wherein R ¹ is 5-cyanopyridin-3-yl, R ⁷ and R ⁸ are hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-3f this table provides 9 compounds A-3f.01 and A-3f.12 having the formula (Ia-A-3) wherein R ¹ is 3-tolyl, R ⁷ and R ⁸ are hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-3G this table provides 9 compounds of formula (Ia-A-3) A-3g.01 and A-3g.12, where R ¹ is 3-phenyl, R ⁷ and R ⁸ are hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-3h this table provides 9 compounds A-3h.01 and A-3h.12 having the formula (Ia-A-3) wherein R ¹ is 3-cyclopropylphenyl, R ⁷ and R ⁸ are hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-3i this table provides 9 compounds A-3i.01 and A-3i.12 of formula (Ia-A-3) wherein R ¹ is 3-cyclopropyl-2-fluorophenyl, R ⁷ is methyl and R ⁸ is hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-3j this table provides 9 compounds A-3j.01 and A-3j.12 of formula (Ia-A-3) wherein R ¹ is 3- (trifluoromethyl) phenyl, R ⁷ is chlorine and R ⁸ is hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-3k this table provides 9 compounds A-3k.01 and A-3k.12 having formula (Ia-A-3) wherein R ¹ is 3- (trifluoromethyl) phenyl, R ⁷ is hydrogen and R ⁸ is fluorine and substituent G is substituent G as defined in Table Z above.

For example, compound A-3k.02 is:

Table A-3l this table provides 9 compounds of formula (Ia-A-3) A-3l.01 and A-3l.12 wherein R ¹ is 5-cyanopyridin-3-yl, R ⁷ is hydrogen and R ⁸ is chlorine and substituent G is substituent G as defined in Table Z above.

Table A-3m this table provides 9 compounds A-3m.01 and A-3m.12 of formula (Ia-A-3) wherein R ¹ is 3-cyclopropylphenyl, R ⁷ is hydrogen and R ⁸ is fluorine and substituent G is substituent G as defined in Table Z above.

Table A-4 Compounds having the formula (Ia-A-4) wherein R ¹、R⁷、R⁸, and R ⁹ are defined in tables A-4a to A-4e and G is defined in Table Z above:

Table A-4a this table provides 9 compounds A-4a.01 and A-4a.12 of the formula (Ia-A-4) wherein R ¹ is 3-cyclopropyl-2-fluorophenyl, R ⁹ is hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-4b this table provides 9 compounds A-4b.01 and A-4b.12 having formula (Ia-A-4) wherein R ¹ is 3- (trifluoromethyl) phenyl, R ⁹ is hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-4c this table provides 9 compounds A-4c.01 and A-4c.12 of formula (Ia-A-4) wherein R ¹ is 5-cyanopyridin-3-yl, R ⁹ is hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-4d this table provides 9 compounds A-4d.01 and A-4d.12 having formula (Ia-A-4) wherein R ¹ is 3-cyclopropylphenyl, R ⁹ is hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-4e this table provides 9 compounds A-4e.01 and A-4e.12 of formula (Ia-A-4) wherein R ¹ is 3-phenyl, R ⁹ is methyl and substituent G is substituent G as defined in Table Z above.

Table A-5 Compounds having the formula (Ia-A-5) wherein R ¹、R⁷、R⁸, and R ⁹ are defined in tables A-5a to A-5G and G is defined in Table Z above:

Table A-5a this table provides 9 compounds A-5a.01 and A-5a.12 of formula (Ia-A-5) wherein R ¹ is 3-cyclopropyl-2-fluorophenyl, R ⁸ is hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-5b this table provides 9 compounds A-5b.01 and A-5b.12 of formula (Ia-A-5) wherein R ¹ is 3- (trifluoromethyl) phenyl, R ⁸ is hydrogen and substituent G is substituent G as defined in Table Z above.

Table A-5c this table provides 9 compounds A-5c.01 and A-5c.12 of formula (Ia-A-5) wherein R ¹ is 5- (cyclopropyl) pyridin-3-yl, R ⁸ is hydrogen and substituent G is as defined in Table Z above.

Table A-5d this table provides 9 compounds A-5d.01 and A-5d.12 of formula (Ia-A-5) wherein R ¹ is 3-cyclopropylphenyl, R ⁸ is hydrogen and substituent G is as defined in Table Z above.

Table A-5e this table provides 9 compounds A-5e.01 and A-5e.12 of formula (Ia-A-5) wherein R ¹ is 3-cyclopropyl-2-fluoro-phenyl R ⁸ is hydrogen and substituent G is as defined in Table Z above.

Table A-5f this table provides 9 compounds A-5f.01 and A-5f.12 of formula (Ia-A-5) wherein R ¹ is 3-phenyl, R ⁸ is chloro and substituent G is as defined in Table Z above.

Table A-5G this table provides 9 compounds of formula (Ia-A-5) A-5g.01 and A-5g.12, where R ¹ is 3-cyclopropylphenyl, R ⁸ is fluorine and substituent G is as defined in Table Z above.

Table A-6 Compounds having the formula (Ia-A-6) wherein R ¹、R⁷、R⁸, and R ⁹ are defined in tables A-6a to A-6c and G is defined in Table Z above:

Table A-6a this table provides 9 compounds A-6a.01 and A-6a.12 of formula (Ia-A-6) wherein R ¹ is 3-cyclopropyl-2-fluorophenyl R ⁷ is hydrogen and substituent G is as defined in Table Z above.

Table A-6b this table provides 9 compounds A-6b.01 and A-6b.12 of formula (Ia-A-6) wherein R ¹ is 3- (trifluoromethyl) phenyl R ⁷ is hydrogen and substituent G is as defined in Table Z above.

Table A-6c this table provides 9 compounds A-6c.01 and A-6c.12 of formula (Ia-A-6) wherein R ¹ is 3-cyclopropylphenyl, R ⁷ is hydrogen and substituent G is as defined in Table Z above.

For example, compound A-6c.06 is:

Table A-7 Compounds having the formula (Ia-A-7) wherein R ¹、R⁷、R⁸, and R ⁹ are defined in tables A-7a to A-7d and G is defined in Table Z above:

Table A-7a this sub-table provides 9 compounds A-7a.01 and A-7a.12 of formula (Ia-A-7) wherein R ¹ is 3-cyclopropyl-2-fluorophenyl, R ⁸ and R ⁹ are hydrogen and substituent G is as defined in Table Z above.

Table A-7b this table provides 9 compounds A-7b.01 and A-7b.12 of formula (Ia-A-7) wherein R ¹ is 3- (trifluoromethyl) phenyl, R ⁸ and R ⁹ are hydrogen and the substituents G are as defined in Table Z above.

Table A-7c this table provides 9 compounds A-7c.01 and A-7c.12 of formula (Ia-A-7) wherein R ¹ is 3-cyclopropylphenyl, R ⁸ and R ⁹ are hydrogen and substituent G is as defined in Table Z above.

Table A-7d this table provides 9 compounds A-7d.01 and A-7d.12 of formula (Ia-A-7) wherein R ¹ is 3-cyclopropyl-2-fluorophenyl, R ⁸ is chloro and R ⁹ is hydrogen and substituent G is as defined in Table Z above.

For example, compound A-7d.04 is:

Table A-7e this table provides 9 compounds A-7e.01 and A-7e.12 of formula (Ia-A-7) wherein R ¹ is 3-cyclopropylphenyl, R ⁸ is fluoro and R ⁹ is hydrogen and substituent G is as defined in Table Z above.

Table A-8 Compounds having the formula (Ia-A-8) wherein R ¹、R⁷、R⁸, and R ⁹ are defined in tables A-8a to A-8f and G is defined in Table Z above:

Table A-8a this sub-table provides 9 compounds A-8a.01 and A-8a.12 of formula (Ia-A-8) wherein R ¹ is 3-cyclopropyl-2-fluorophenyl, R ⁷ and R ⁹ are hydrogen and substituent G is as defined in Table Z above.

Table A-8b this table provides 9 compounds A-8b.01 and A-8b.12 of formula (Ia-A-8) wherein R ¹ is 3- (trifluoromethyl) phenyl, R ⁷ and R ⁹ are hydrogen and the substituents G are as defined in Table Z above.

Table A-8c this sub-table provides 9 compounds A-8c.01 and A-8c.12 of formula (Ia-A-8) wherein R ¹ is 5-cyanopyridin-3-yl, R ⁷ and R ⁹ are hydrogen and substituent G is as defined in Table Z above.

Table A-8d this table provides 9 compounds A-8d.01 and A-8d.12 of formula (Ia-A-8) wherein R ¹ is 3-tolyl, R ⁷ and R ⁹ are hydrogen and the substituents G are as defined in Table Z above.

Table A-8e this table provides 9 compounds A-8e.01 and A-8e.12 of formula (Ia-A-8) wherein R ¹ is 3-cyclopropylphenyl, R ⁷ and R ⁹ are hydrogen and substituent G is as defined in Table Z above.

Table A-8f this table provides 9 compounds A-8f.01 and A-8f.12 of formula (Ia-A-8) wherein R ¹ is 3-cyclopropylphenyl, R ⁷ is hydrogen, R ⁹ is methyl and substituent G is as defined in Table Z above.

For example, compound A-8f.5 is:

Table A-9 Compounds having the formula (Ia-A-9) wherein R ¹、R⁷、R⁸, and R ⁹ are defined in tables A-9a to A-9d and G is defined in Table Z above:

Table A-9a this table provides 9 compounds A-9a.01 and A-9a.12 having the formula (Ia-A-9) wherein R ¹ is 3-cyclopropyl-2-fluorophenyl, R ⁷ and R ⁸ are hydrogen and substituent G is as defined in Table Z above.

Table A-9b this table provides 9 compounds A-9b.01 and A-9b.12 having the formula (Ia-A-9) wherein R ¹ is 3- (trifluoromethyl) phenyl, R ⁷ and R ⁸ are hydrogen and the substituents G are as defined in Table Z above.

Table A-9c this table provides 9 compounds A-9c.01 and A-9c.12 having the formula (Ia-A-9) wherein R ¹ is 3-phenyl, R ⁷ and R ⁸ are hydrogen and substituent G is as defined in Table Z above.

For example, compound A-9c.7 is:

Table A-9d this table provides 9 compounds A-9d.01 and A-9d.12 having the formula (Ia-A-9) wherein R ¹ is 3-cyclopropylphenyl, R ⁷ and R ⁸ are hydrogen and substituent G is as defined in Table Z above.

Table A-10 Compounds having the formula (Ia-A-10) wherein R ¹、R⁷、R⁸, and R ⁹ are defined in tables A-10a to A-10c and G is defined in Table Z above:

Table A-10a this sub-table provides 9 compounds A-10a.01 and A-10a.12 of formula (Ia-A-10) wherein R ¹ is 3-cyclopropyl-2-fluorophenyl R ⁹ is hydrogen and substituent G is as defined in Table Z above.

Table A-10b this table provides 9 compounds A-10b.01 and A-10b.12 of formula (Ia-A-10) wherein R ¹ is 3- (trifluoromethyl) phenyl R ⁹ is hydrogen and substituent G is as defined in Table Z above.

For example, compound A-10b.4 is:

Table A-10c this table provides 9 compounds A-10c.01 and A-10c.12 of formula (Ia-A-10) wherein R ¹ is 3-cyclopropylphenyl, R ⁹ is hydrogen and substituent G is as defined in Table Z above.

Table A-11 Compounds having the formula (Ia-A-11) wherein R ¹、R⁷、R⁸, and R ⁹ are defined in tables A-11a to A-11c and G is defined in Table Z above:

Table A-11a this table provides 9 compounds A-11a.01 and A-11a.12 of formula (Ia-A-11) wherein R ¹ is 3-cyclopropyl-2-fluorophenyl R ⁷ is hydrogen and the substituents G are as defined in Table Z above.

Table A-11b this table provides 9 compounds A-11b.01 and A-11b.12 of formula (Ia-A-11) wherein R ¹ is 3- (trifluoromethoxy) phenyl R ⁷ is hydrogen and substituent G is as defined in Table Z above.

Table A-11c this table provides 293 compounds A-11c.01 and A-11c.12 of formula (Ia-A-11) wherein R ¹ is 3-cyclopropylphenyl, R ⁷ is hydrogen and substituent G is as defined in Table Z above.

Table A-12 Compounds having the formula (Ia-A-12) wherein R ¹、R⁷、R⁸, and R ⁹ are defined in tables A-12a to A-12c and G is defined in Table Z above:

Table A-12a this table provides 9 compounds A-12a.01 and A-12a.12 of formula (Ia-A-12) wherein R ¹ is 3-cyclopropyl-2-fluorophenyl R ⁸ is hydrogen and substituent G is as defined in Table Z above.

Table A-12b this table provides 9 compounds A-12b.01 and A-12b.12 of formula (Ia-A-12) wherein R ¹ is 3-tolyl, R ⁸ is hydrogen and substituent G is as defined in Table Z above.

Table A-12c this table provides 9 compounds A-12c.01 and A-12c.12 of formula (Ia-A-12) wherein R ¹ is 3-cyclopropylphenyl, R ⁸ is chloro and substituent G is as defined in Table Z above.

Table A-13 Compounds having the formula (Ia-A-13) wherein R ¹、R⁷、R⁸, and R ⁹ are defined in tables A-13a to A-13b and G is defined in Table Z above:

Table A-13a this table provides 9 compounds A-13a.01 and A-13a.12 of formula (Ia-A-13) wherein R ¹ is 3-cyclopropyl-2-fluorophenyl, R ⁸ and R ⁹ are hydrogen and substituent G is as defined in Table Z above.

Table A-13b this table provides 9 compounds A-13b.01 and A-13b.12 of formula (Ia-A-13) wherein R ¹ is 3-phenyl, R ⁸ is methyl and R ⁹ is hydrogen and substituent G is as defined in Table Z above.

Table A-14 Compounds having the formula (Ia-A-14) wherein R ¹、R⁷、R⁸, and R ⁹ are defined in tables A-14a to A-14f and G is defined in Table Z above:

Table A-14a this sub-table provides 9 compounds A-14a.01 and A-14a.12 of formula (Ia-A-14) wherein R ¹ is 3-cyclopropyl-2-fluorophenyl, R ⁷ and R ⁹ are hydrogen and substituent G is as defined in Table Z above.

Table A-14b this table provides 9 compounds A-14b.01 and A-14b.12 of formula (Ia-A-14) wherein R ¹ is 3- (trifluoromethyl) phenyl, R ⁷ and R ⁹ are hydrogen and the substituents G are as defined in Table Z above.

Table A-14c this sub-table provides 9 compounds A-14c.01 and A-14c.12 of formula (Ia-A-14) wherein R ¹ is 5-cyanopyridin-3-yl, R ⁷ and R ⁹ are hydrogen and substituent G is as defined in Table Z above.

Table A-14d this table provides 9 compounds A-14d.01 and A-14d.12 of formula (Ia-A-14) wherein R ¹ is 3-cyclopropylphenyl, R ⁷ and R ⁹ are hydrogen and substituent G is as defined in Table Z above.

Table A-14e this table provides 9 compounds A-14e.01 and A-14e.12 of formula (Ia-A-14) wherein R ¹ is 3-cyclopropyl-2-fluorophenyl, R ⁷ is methyl, R ⁹ is methyl and the substituents G are as defined in Table Z above.

Table A-14f this table provides 9 compounds A-14f.01 and A-14f.12 of formula (Ia-A-14) wherein R ¹ is 3-phenyl, R ⁷ is hydrogen, R ⁹ is methyl and substituent G is as defined in Table Z above.

Table A-15 Compounds having the formula (Ia-A-15) wherein R ¹、R⁷、R⁸, and R ⁹ are defined in tables A-15a to A-15f and G is defined in Table Z above:

Table A-15a this table provides 9 compounds A-15a.01 and A-15a.12 of formula (Ia-A-15) wherein R ¹ is 3-cyclopropyl-2-fluorophenyl, R ⁷ and R ⁸ are hydrogen and substituent G is as defined in Table Z above.

Table A-15b this table provides 9 compounds A-15b.01 and A-15b.12 of formula (Ia-A-15) wherein R ¹ is 3- (trifluoromethyl) phenyl, R ⁷ and R ⁸ are hydrogen and the substituents G are as defined in Table Z above.

Table A-15c this sub-table provides 9 compounds A-15c.01 and A-15c.12 of formula (Ia-A-15) wherein R ¹ is 5-cyanopyridin-3-yl, R ⁷ and R ⁸ are hydrogen and substituent G is as defined in Table Z above.

Table A-15d this table provides 9 compounds A-15d.01 and A-15d.12 of formula (Ia-A-15) wherein R ¹ is 5- (cyclopropyl) pyridin-3-yl, R ⁷ and R ⁸ are hydrogen and substituent G is as defined in Table Z above.

Table A-15e this table provides 9 compounds A-15e.01 and A-15e.12 of formula (Ia-A-15) wherein R ¹ is 3-cyclopropyl-2-fluorophenyl, R ⁷ is hydrogen and R ⁸ is fluoro and substituent G is as defined in Table Z above.

Tables A-15f this table provides 9 compounds A-15f.01 and A-15f.12 of formula (Ia-A-15) wherein R ¹ is 3-cyclopropylphenyl, R ⁷ is methyl and R ⁸ is hydrogen and substituent G is as defined in Table Z above.

Table A-16 Compounds having the formula (Ia-A-16) wherein R ¹、R⁷、R⁸, and R ⁹ are defined in tables A-16a to A-16c and G is defined in Table Z above:

Table A-16a this table provides 9 compounds A-16a.01 and A-16a.12 of formula (Ia-A-16) wherein R ¹ is 3-cyclopropyl-2-fluorophenyl R ⁷ is hydrogen and the substituents G are as defined in Table Z above.

Table A-16b this table provides 9 compounds A-16b.01 and A-16b.12 of formula (Ia-A-16) wherein R ¹ is 3- (trifluoromethyl) phenyl R ⁷ is hydrogen and substituent G is as defined in Table Z above.

Table A-16c this sub-table provides 9 compounds A-16c.01 and A-16c.12 of formula (Ia-A-16) wherein R ¹ is 5-cyanopyridin-3-yl, R ⁷ is hydrogen and substituent G is as defined in Table Z above.

Table A-17 Compounds having the formula (Ia-A-17) wherein R ¹、R⁷、R⁸, and R ⁹ are defined in tables A-17a to A-17c and G is defined in Table Z above:

Table A-17a this table provides 9 compounds A-17a.01 and A-17a.12 of formula (Ia-A-17) wherein R ¹ is 3-cyclopropyl-2-fluorophenyl R ⁸ is hydrogen and the substituents G are as defined in Table Z above.

Table A-17b this table provides 9 compounds A-17b.01 and A-17b.12 of formula (Ia-A-17) wherein R ¹ is 3- (trifluoromethyl) phenyl R ⁸ is hydrogen and substituent G is as defined in Table Z above.

Table A-17c this table provides 9 compounds A-17c.01 and A-17c.12 of formula (Ia-A-17) wherein R ¹ is 3-tolyl, R ⁸ is hydrogen and substituent G is as defined in Table Z above.

It also makes available certain intermediate compounds having the formulae (IC-1), (IC-2) and (IC-3), some of which are novel:

wherein R ¹、Q^a、Q^b、Q^c、Q⁷、Q⁸、Q⁹, and G are as defined above for compounds having formula (I);

X ^a is X ³ or X ⁴;

X ^b and X ^c are both hydrogen, or X ^b is hydrogen and X ^c is a protecting group selected from t-butyloxycarbonyl, benzylcarbonyl, 9-fluorenylmethylcarbonyl, trifluoroacetyl, benzyl, triphenylmethyl, benzylidene, and p-toluenesulfonyl, or X ^b and X ^c are the same or different protecting groups, or X ^b and X ^c together with the nitrogen to which they are attached form a protecting group, wherein the protecting group is selected from t-butyloxycarbonyl, benzylcarbonyl, 9-fluorenylmethylcarbonyl, trifluoroacetyl, benzyl, triphenylmethyl, benzylidene, p-toluenesulfonyl, phthalimide, or succinimide, or;

X ^d is H or-CH ₂-C(O)-CH₂ -G;

x ³ is a leaving group selected from fluorine, chlorine, bromine, iodine, BF ₃K、B(OH)₂ and B (pinacol);

X ⁴ is OH or-O-R ¹.

As can be seen from the above formulae for the intermediate compounds of formulae (IC-1), (IC-2) and (IC-3), the heterobicyclic groupCorresponds to group a as defined for compounds having formula (Ia), wherein # denotes a bond to X ^a in an intermediate compound having formulae (IC-1) and (IC-2) or to X ⁴ in an intermediate compound having formula (IC-3), and% denotes a bond to an amide group of an intermediate compound having formula (IC-1), to a-5, 6-dihydro-4H-1, 2, 4-oxadiazin-3-yl-G moiety in an intermediate compound having formula (IC-2), or to an amidine in an intermediate compound having formula (IC-3).

In the intermediate compounds having the formulas (IC-1), (IC-2) and (IC-3), the group A may be as defined in tables 1 and 2. Preferably, A is A-1, A-2, A-3, A-5, A-14 or A-15. More preferably, A is A-3, A-5 or A-15. In particular, A and R ¹ are as defined in tables A-1 to A-17 and their corresponding sub-tables, and G is as defined in Table Z. Preferably, A and R ¹ are as defined in tables A-1, A-2, A-3, A-5, A-14 or A-15 and their corresponding sub-tables, and G is as defined in Table Z. More preferably, A and R ¹ are as defined in tables A-3, A-5 or A-15 and their corresponding sub-tables, and G is as defined in Table Z.

For example, it is made possible to obtain certain intermediate compounds having the formulae (II), (X) and (XV). They correspond to intermediate compounds of formula (IC-1) in which X ^b and X ^c are both hydrogen and X ^a is O-R ¹ in compounds of formula (II), X ³ in compounds of formula (X), or OH in compounds of formula (XV):

Wherein R ¹、Q^a、Q^b、Q^c、Q⁷、Q⁸、Q⁹, and G are as defined above for a compound of formula (I), and X ³ is a leaving group selected from fluorine, chlorine, bromine, iodine, BF ₃K、B(OH)₂ and B (pinacol). In particular, G is as defined in table Z.

It also makes available certain other intermediate compounds of formulae (III), (IX) and (XIV). They correspond to intermediate compounds of formula (IC-1), wherein X ^a is O-R ¹ in the compound of formula (III), X ³ in the compound of formula (IX), or OH in the compound of formula (XIV), and wherein X ^b and X ^c are X ¹ and X ², respectively:

Wherein R ¹、Q^a、Q^b、Q^c、Q⁷、Q⁸、Q⁹, and G are as defined above for a compound having formula (I), in particular G is as defined in Table Z, X ¹ is H and X ² is a protecting group, or X ¹ and X ² are the same or different protecting groups, or X ¹ and X ² together with the nitrogen to which they are attached form a protecting group. Examples of protecting groups include, for example, t-butyloxycarbonyl, benzylcarbonyl, 9-fluorenylmethylcarbonyl, trifluoroacetyl, benzyl, triphenylmethyl, benzylidene, p-toluenesulfonyl, phthalimide, or succinimide.

It also makes available certain other intermediate compounds of the formulae (VIII), (XIII) and (XVII). They correspond to intermediate compounds of formula (IC-2) in which X ^a is X ³ in the compound of formula (VIII), OH in the compound of formula (XIII), or X ⁴ in the compound of formula (XVII):

Wherein R ¹、Q^a、Q^b、Q^c、Q⁷、Q⁸、Q⁹, and G are as defined above for a compound having formula (I), in particular G is as defined in Table Z, X ³ is a leaving group selected from fluorine, chlorine, bromine, iodine, BF ₃K、B(OH)₂ and B (pinacol), and X ⁴ is OH or-O-R ¹.

It also makes available certain other intermediate compounds having the formulae (XXII) and (XXIII). They correspond to intermediate compounds of the formula (IC-3), where X ^d is-CH ₂-C(O)-CH₂ -G in the compound of the formula (XXII) or H in the compound of the formula (XXIII):

Wherein R ¹、Q^a、Q^b、Q^c、Q⁷、Q⁸、Q⁹, and G are as defined above for compounds of formula (I), in particular G is as defined in Table Z, and X ⁴ is OH or-O-R ¹.

In intermediate compounds having the formulae (II), (III), (VIII), (IX), (X), (XIII), (XIV), (XV), (XVII), (XXII) and (XXIII), the group a can be as defined in tables 1 and 2. Preferably, A is A-1, A-2, A-3, A-5, A-14 or A-15. More preferably, A is A-3, A-5 or A-15. In particular, A and R ¹ are as defined in tables A-1 to A-17 and their corresponding sub-tables, and G is as defined in Table Z. Preferably, A and R ¹ are as defined in tables A-1, A-2, A-3, A-5, A-14 or A-15 and their corresponding sub-tables, and G is as defined in Table Z. More preferably, A and R ¹ are as defined in tables A-3, A-5 or A-15 and their corresponding sub-tables, and G is as defined in Table Z. X ^a、X^b、X^c、X^d、X³ and X ⁴ are as defined above for the compounds of the formulae (IC-1), (IC-2), and (IC-3).

For example, the following intermediate compounds are made available, some of which are new:

-a compound of formula (II) wherein R ¹ and a are as defined in any of tables a-1 to a-17 and their counterparts, and G is as defined in table Z:

And more particularly compounds having the formulae (II-a-1 i) to (II-a-17 i), as shown in table II below, wherein R ¹、R⁷、R⁸, and R ⁹ are as defined in any one of tables a-1 to a-17 and their counterparts, and G is as defined in table Z:

Table II

-A compound of formula (III) wherein X ¹ and X ² are the same or different protecting groups selected from t-butyloxycarbonyl, benzylcarbonyl, 9-fluorenylmethylcarbonyl, trifluoroacetyl, benzyl, phthaloyl, triphenylmethyl, benzylidene and p-toluenesulfonyl, or X ¹ and X ² together with the nitrogen to which they are attached form a protecting ring, and wherein R ¹ and a are as defined in any one of tables a-1 to a-17 and their corresponding sub-tables, and G is as defined in table Z:

And more particularly compounds having the formulae (III-a-1 i) to (III-a-17 i), as shown in table III below, wherein R ¹、R⁷、R⁸, and R ⁹ are as defined in any one of tables a-1 to a-17 and their counterparts, and G is as defined in table Z:

Table III

-A compound of formula (VIII) wherein X ³ is a suitable leaving group such as fluoro, chloro, bromo, iodo, BF ₃K、B(OH)₂ or B (pinacol), and wherein a is as defined in any one of tables a-1 to a-17 and their counterparts, and G is as defined in table Z:

And more particularly compounds having the formulae (VIII-a-1 i) to (VIII-a-17 i), as shown in table VIII below, wherein R ⁷、R⁸, and R ⁹ are defined in any one of tables a-1 to a-17 and their counterparts, and G is defined in table Z:

Table VIII

-A compound of formula (IX) wherein X ¹ and X ² are the same or different protecting groups selected from t-butyloxycarbonyl, benzylcarbonyl, 9-fluorenylmethylcarbonyl, trifluoroacetyl, benzyl, phthaloyl, triphenylmethyl, benzylidene and p-toluenesulfonyl, or X ¹ and X ² together with the nitrogen to which they are attached form a protecting ring, X ³ is a suitable leaving group such as fluorine, chlorine, bromine, iodine, BF ₃K、B(OH)₂ or B (pinacol), and wherein a is as defined in any one of tables a-1 to a-17 and their corresponding sub-tables, and G is as defined in table Z:

and more particularly compounds having the formulae (IX-A-1 i) to (IX-A-17 i), as shown in Table IX below, wherein R ⁷、R⁸, and R ⁹ are defined in any one of tables A-1 to A-17 and their corresponding sub-tables, and G is defined in Table Z:

Table IX

-A compound of formula (X) wherein X ³ is a suitable leaving group such as fluoro, chloro, bromo, iodo, BF ₃K、B(OH)₂ or B (pinacol), and wherein a is as defined in any one of tables a-1 to a-17 and their counterparts, and G is as defined in table Z:

And more particularly compounds having the formulae (X-a-1 i) to (X-a-17 i), as shown in table X below, wherein R ⁷、R⁸, and R ⁹ are defined in any one of tables a-1 to a-17 and their counterparts, and G is defined in table Z:

Table X

-A compound of formula (XIII) wherein a is as defined in any one of tables a-1 to a-17 and their counterparts, and G is as defined in table Z:

And more particularly compounds having the formulae (XIII-a-1 i) to (XIII-a-17 i), as shown in table XIII below, wherein R ⁷、R⁸, and R ⁹ are as defined in any one of tables a-1 to a-17 and their counterparts, and G is as defined in table Z:

Table XIII

-A compound of formula (XIV) wherein X ¹ and X ² are the same or different protecting groups selected from t-butyloxycarbonyl, benzylcarbonyl, 9-fluorenylmethylcarbonyl, trifluoroacetyl, benzyl, phthaloyl, triphenylmethyl, benzylidene and p-toluenesulfonyl, or X ¹ and X ² together with the nitrogen to which they are attached form a protecting ring, and a is as defined in any one of tables a-1 to a-17 and their corresponding sub-tables, and G is as defined in table Z:

And more particularly compounds having the formulae (XIV-A-1 i) to (XIV-A-17 i), as shown in table XIV below, wherein R ⁷、R⁸, and R ⁹ are defined in any one of tables A-1 to A-17 and their counterparts, and G is defined in table Z:

Table XIV

-A compound of formula (XV), wherein a is as defined in any one of tables a-1 to a-17 and their counterparts, and G is as defined in table Z:

And more particularly compounds having the formulae (XV-A-1 i) to (XV-A-17 i), as shown in table XV below, wherein R ⁷、R⁸, and R ⁹ are defined in any one of tables A-1 to A-17 and their corresponding sub-tables, and G is defined in table Z:

table XV

-A compound of formula (XVII) wherein a and R ¹ are as defined in any one of tables a-1 to a-17 and their counterparts and G is as defined in table Z:

And more particularly compounds having the formulae (XVII-A-1 i) to (XVII-A-17 i), as shown in Table XVII below, wherein R ¹、R⁷、R⁸, and R ⁹ are as defined in any of tables A-1 to A-17 and their counterparts, and G is as defined in Table Z:

Table XVII

-A compound of formula (XXII), wherein X ⁴ is OH or-O-R ¹, and wherein a is as defined in any one of tables a-1 to a-17 and their counterparts, and G is as defined in table Z:

And more particularly compounds having the formulae (XXII-a-1 i) to (XXII-a-17 i), as shown in table XXII below, wherein R ⁷、R⁸, and R ⁹ are as defined in any one of tables a-1 to a-17 and their counterparts, and G is as defined in table Z:

table XXII

-A compound of formula (XXIII), wherein X ⁴ is OH or-O-R ¹, and wherein a is as defined in any one of tables a-1 to a-17 and their counterparts, and G is as defined in table Z:

And more particularly compounds having the formulae (XXIII-a-1 i) to (XXIII-a-17 i), as shown in table XXIII below, wherein R ⁷、R⁸, and R ⁹ are as defined in any one of tables a-1 to a-17 and their counterparts, and G is as defined in table Z:

Table XXIII

Thus, in a further aspect, the invention makes it possible to obtain intermediate compounds of the formulae (IC-1), (IC-2) and (IC-3), such as compounds of the formulae (II), (III), (VIII), (IX), (X), (XIII), (XIV), (XV), (XVII), (XXII) and (XXIII), where in each case R ¹、Q^a、Q^b、Q^c、Q⁷、Q⁸、Q⁹, and G, including R ⁷、R⁸, And R ⁹ as defined for a compound of formula (I) in the first aspect, or any of the embodiments described above, and X ^a is X ³ or X ⁴;X^b and X ^c are both hydrogen, or X ^b is hydrogen and X ^c is a protecting group, or X ^b and X ^c are the same or different protecting groups, or X ^b and X ^c together with the nitrogen to which they are attached form a protecting group, wherein the one or more protecting groups are selected from tert-butyloxycarbonyl, and a pharmaceutically acceptable salt of a compound of formula (I), Benzylcarbonyl, 9-fluorenylmethylcarbonyl, trifluoroacetyl, benzyl, triphenylmethyl, benzylidene, p-toluenesulfonyl, phthalimide, and succinimide, X ^d is H or-CH ₂-C(O)-CH₂-G;X³ is a leaving group selected from fluorine, chlorine, bromine, iodine, BF ₃K、B(OH)₂, and B (pinacol), and X ⁴ is OH or-O-R ¹. In particular, Q ^a、Q^b、Q^c、Q⁷、Q⁸、Q⁹ is as defined in Table 1 or Table 2, preferably Q ^a、Q^b、Q^c、Q⁷、Q⁸、Q⁹ has the definition as given for A-1, A-2, A-3, A-5, A-14 or A-15, more preferably Q ^a、Q^b、Q^c、Q⁷、Q⁸、Q⁹ has the definition as given for A-3, a-5 or A-15.

Examples

The following examples are intended to illustrate the invention and are not meant to limit the invention in any way.

The compounds of the invention may differ from the known compounds in greater efficacy at low administration rates, as demonstrated by one of ordinary skill in the art using the experimental procedures outlined in the examples, using lower administration rates (if necessary) such as 60ppm, 20ppm or 2 ppm.

The compounds having formula (I) may have any number of benefits, including in particular advantageous levels of biological activity for protecting plants from diseases caused by fungi or superior properties for use as agrochemical active ingredients (e.g. higher biological activity, advantageous activity profile, increased safety (including improved crop tolerance), improved physico-chemical properties, or increased biodegradability).

Throughout this specification, temperature is given in degrees celsius and "m.p." means melting point. LC/MS means liquid chromatography mass spectrometry, and the description of the apparatus and method is as follows.

¹ H NMR and ¹⁹ F NMR measurements were recorded on a Bruker 400MHz spectrometer, and chemical shifts were given in ppm relative to TMS (¹ H) and CFCl3 (¹⁹ F) standards. The spectra were measured in deuterated solvents as indicated. These compounds were characterized by any of the following LC-MS methods. The characteristic LC-MS values obtained for each compound are retention time ("Rt", recorded in minutes) and the measured molecular ion (m+h) ⁺ or (M-H) ^-.

Examples of formulations

The combination is thoroughly mixed with these adjuvants and the mixture is thoroughly ground in a suitable mill, so that a wettable powder is obtained which can be diluted with water to give a suspension of the desired concentration.

The combination is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable grinder, so that a powder is obtained which can be used directly for seed treatment.

Emulsifiable concentrate

Emulsions with any desired dilution that can be used in plant protection can be obtained from such concentrates by dilution with water.

A ready-to-use dust powder is obtained by mixing the combination with a carrier and grinding the mixture in a suitable grinder. Such dust can also be used for dry dressing of seeds.

Extruder granule

The combination is mixed and ground with these adjuvants and the mixture is moistened with water. The mixture was extruded and then dried in an air stream.

Coated granule

Active ingredient 8%

Polyethylene glycol (molar weight 200) 3%

Kaolin 89%

The finely ground combination is applied uniformly in a mixer to kaolin wet with polyethylene glycol. In this way dust-free coated granules are obtained.

Suspension concentrate

The finely ground combination is intimately mixed with the adjuvants to give a suspension concentrate from which any desired dilution of the suspension can be obtained by dilution with water. With such dilutions, living plants can be treated together with plant propagation material and protected against infestation by microorganisms by spraying, watering or dipping.

Flowable concentrate for seed treatment

Sustained release capsule suspension

28 Parts of the combination are mixed with 2 parts of aromatic solvent and 7 parts of toluene diisocyanate/polymethylene-polyphenyl isocyanate-mixture (8:1). This mixture was emulsified in a mixture of 1.2 parts of polyvinyl alcohol, 0.05 parts of defoamer and 51.6 parts of water until the desired particle size was reached. To this emulsion was added 2.8 parts of a1, 6-hexamethylenediamine mixture in 5.3 parts of water. The mixture was stirred until the polymerization was completed. The capsule suspension obtained is stabilized by adding 0.25 parts of thickener and 3 parts of dispersant. The capsule suspension formulation contains 28% active ingredient. The diameter of the media capsule is 8-15 microns. The resulting formulation is applied to the seeds as an aqueous suspension in a device suitable for the purpose.

Formulation types include Emulsion Concentrates (EC), suspension Concentrates (SC), suspoemulsions (SE), capsule Suspensions (CS), water dispersible granules (WG), emulsifiable Granules (EG), emulsions, water-in-oil Emulsions (EO), oil-in-water Emulsions (EW), microemulsions (ME), oil Dispersions (OD), oil suspensions (OF), oil-soluble solutions (OL), soluble concentrates (SL), ultra-low volume Suspensions (SU), ultra-low volume solutions (UL), parent drugs (TK), dispersible Concentrates (DC), wettable Powders (WP), soluble Granules (SG) or any technically feasible formulation in combination with agriculturally acceptable adjuvants.

Abbreviations (abbreviations)

Abbreviations for synthetic schemes and preparation examples

ACN acetonitrile (AcN or MeCN)

Aq. aqueous

Boc t-Butoxycarbonyl group

CDCl ₃ deuterated chloroform

DBU 1, 8-diazabicyclo [5.4.0] undec-7-ene

DCM dichloromethane

DDQ 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone

DMSO dimethyl sulfoxide

DMSO-d6 deuterated dimethyl sulfoxide

DPEN diphenyl ethylenediamine

Et ₃ N triethylamine

EtOAc ethyl acetate

HATU 1- [ bis (dimethylamino) methylene ] -1H-1,2, 3-triazolo [4,5-b ] pyridinium-3-oxide-hexafluorophosphate

HCl hydrochloric acid

H/hrs hours

MeCN acetonitrile

MeOH ethanol

Ms methanesulfonyl group (methylsulfonyl)

N-Bu n-butyl

NHC N-heterocyclic carbenes

NPhth phthalimide-1-yl

OMs mesylate groups

OTf triflate group

OTs tosylate radical

PdCl2dppf 1,1' -bis (diphenylphosphino) ferrocene ] palladium (II) dichloride

Rt room temperature

T3P propane phosphonic acid anhydride, also known as 2,4, 6-tripropyl-1,3,5,2,4,6-trioxal

TBME triphosphohexane-2, 4, 6-trioxyde tert-butyl methyl ether

TEA triethylamine

TEMPO (2, 6-tetramethylpiperidin-1-yl) oxy-nitrogen radical

Tf trifluoromethanesulfonyl (trifluoromethanesulfonyl)

TFA trifluoroacetic acid

THF tetrahydrofuran

TLC thin layer chromatography

Ts p-toluenesulfonyl (tosyl)

X-Phos 2-dicyclohexylphosphino-2 ',4',6' -triisopropylbiphenyl

Preparation example

The compounds of formula (I) according to the invention can be prepared using the synthetic techniques described above and below.

"Mp" means the melting point in degrees Celsius. The radical represents a methyl group. ¹ H NMR and ¹⁹ F NMR measurements were recorded on a Bruker400MHz spectrometer (or 600MHz as indicated), chemical shifts are given in ppm relative to TMS (¹ H) and CFCl ₃(¹⁹ F standards. The spectra were measured in deuterated solvents as indicated. These compounds were characterized by any of the following LC-MS methods. The characteristic LC-MS values obtained for each compound are retention time ("Rt", recorded in minutes) and the measured molecular ion (m+h) ⁺ or (M-H) ^-.

Unless otherwise indicated, ¹ H NMR spectra were recorded at 400MHz and ¹⁹ f NMR spectra were recorded at 377MHz, and chemical shifts were recorded in ppm. The following abbreviations are used: s = unimodal; br s = broad peak; d = double peak; brd=broad doublet, dd=doublet, dt=doublet, t=triplet, tt=triplet, q=quartet, quin=quin, sept =heptad, m=multiplet.

Throughout this specification, temperature is given in degrees celsius (°c). "MP" means melting point. "Rt" means retention time. LC/MS means liquid chromatography mass spectrometry. The LC/MS apparatus and method are:

LC-MS method A. Spectra were recorded on a mass spectrometer (6410 triple quadrupole mass spectrometer) from Agilent technologies Co (Agilent Technologies) equipped with an electrospray source (positive and negative polarity conversion, capillary voltage (kV) 4.00, scanning type MS2 scan, fragmentation voltage (V) 100.00, gas temperature (° C): 350, gas flow (L/min): 11, nebulizer gas (psi): 45, mass range: 110Da to 1000 Da) and Agilent 1200 series HPLC: DAD wavelength range: 210 to 400nm, column: KINETEX EVO C, column length: 50mm, column inner diameter: 4.6mm, particle size: 2.6 μm, column box temperature: 40 ℃ C

Gradient conditions:

Solvent A water containing 0.1% formic acid, acetonitrile 95:5v/v

Solvent B acetonitrile containing 0.1% formic acid

If desired, the final compounds pure in the enantiomeric sense can be obtained from the racemic material via standard physical separation techniques (e.g., reverse phase chiral chromatography) or by stereoselective synthesis techniques (e.g., by using chiral starting materials), as appropriate.

LC-MS method B spectra were recorded on a mass spectrometer (6410 triple quadrupole mass spectrometer) from Agilent technologies company equipped with an electrospray source (positive and negative polarity conversion, capillary voltage (kV) 7.00, scanning type MS2 scan, fragmentation voltage (V) 120.00, gas temperature (° C): 350, gas flow (L/min): 11, nebulizer gas (psi): 40, mass range: 110Da to 650 Da) and Agilent 1200 series HPLC: DAD wavelength: 254nm, column: KINETEX EVO C, column length: 50mm, column inner diameter: 4.6mm, particle size: 2.6 μm, column box temperature: 40 ℃

Gradient conditions:

Solvent A water containing 0.1% formic acid, acetonitrile 95:5v/v

Solvent B acetonitrile containing 0.1% formic acid

LC-MS method C spectra were recorded on a mass spectrometer (Acquisy QDA Mass spectrometer) from Waters, inc., equipped with an electrospray source (positive and negative polarity conversion, capillary voltage (kV) 0.8, cone voltage (V) 25.00, full scan, source temperature (° C): 120, desolvation gas flow (L/Hr): 1000, desolvation temperature (° C): 600, cone gas flow (L/Hr): 50, mass range: 110Da to 850 Da) and HPLC: DAD wavelength range: 230 to 400nm, column Acquity UPLC HSS T C18, column length: 30mm, column inner diameter: 2.1mm, particle size: 1.8 μm, column box temperature: 40 ℃ C.)

Gradient conditions:

Solvent A water containing 0.1% formic acid, acetonitrile 95:5v/v

Solvent B acetonitrile containing 0.05% formic acid

LC-MS method D spectra were recorded on a mass spectrometer (acquisition SDQ mass spectrometer) from Waters company equipped with an electrospray source (positive and negative polarity conversion, capillary voltage (kV) 3.0, full scan, cone voltage (V) 41.0, source temperature (° C): 150, desolvation temperature: (° C) 500, cone gas flow (L/Hr): 50, mass range: 110Da to 800 Da) and HPLC 'H' grade: DAD wavelength range: 210 to 400nm, column Acquity UPLC HSS T C18, column length: 30mm, column inner diameter: 2.1mm, particle size: 1.8 μm, column box temperature: 40 ℃ C.)

Gradient conditions:

Solvent A water containing 0.1% formic acid, acetonitrile 95:5v/v

Solvent B acetonitrile containing 0.05% formic acid

Example P1 preparation of 3- [6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidin-7-yl ] -5- [ (2, 4-dichlorophenyl) methyl ] -5, 6-dihydro-4H-1, 2, 4-oxadiazine (compound 1.1 of Table T1)

(Compound 1.1 of Table T1)

A) Preparation of ethyl 2- (3-cyclopropylphenoxy) acetate

Cesium carbonate (5.82 g,17.8 mmol) was added to a solution of 3-cyclopropylphenol (2.0 g,14.9 mmol) in acetonitrile (22 mL) in a single neck round bottom flask. Ethyl 2-bromoacetate (2.98 g,17.8 mmol) was added thereto and the resulting reaction mixture was stirred at room temperature for 4 hours. The progress of the reaction was monitored by LCMS. The reaction mixture was then diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure to obtain a crude residue. The resulting crude residue was purified by silica gel chromatography (cyclohexane/ethyl acetate) to give ethyl 2- (3-cyclopropylphenoxy) acetate (1.7 g, 41%).

LCMS (method B) retention time 1.48min,221 (M+H)

B) Preparation of ethyl 2- (3-cyclopropylphenoxy) -3- (dimethylamino) prop-2-enoate

In a sealed glass reactor, ethyl 2- (3-cyclopropylphenoxy) acetate (1.5 g,6.8 mmol) and 1-tert-butoxy-N, N, N ', N' -tetramethyl-methyldiamine (9.2 g,48.0 mmol) were heated to 90℃for 2 hours. The progress of the reaction was monitored by LCMS. The reaction mixture was then diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure to obtain a crude residue. The resulting crude residue was purified by silica gel chromatography (cyclohexane/ethyl acetate) to give ethyl 2- (3-cyclopropylphenoxy) -3- (dimethylamino) prop-2-enoate (1.47 g, 78%).

LCMS (method B) retention time 1.52min,276 (M+H)

C) Preparation of 6- (3-cyclopropylphenoxy) -4H-pyrazolo [1,5-a ] pyrimidin-7-one

In a single neck round bottom flask, a mixture of ethyl 2- (3-cyclopropylphenoxy) -3- (dimethylamino) prop-2-enoate (1.0 g,3.63 mmol), 3H-pyrazol-3-amine (0.30 g,3.63 mmol) and sodium acetate (0.30 g,3.63 mmol) was stirred in acetic acid (2 mL) at 90℃for 24 hours. The progress of the reaction was monitored by LCMS. After the completion of the reaction, the reaction mixture was concentrated under reduced pressure, and co-distilled with toluene twice under reduced pressure to obtain a crude mixture, which was purified by silica gel chromatography (cyclohexane/ethyl acetate) to give 6- (3-cyclopropylphenoxy) -4H-pyrazolo [1,5-a ] pyrimidin-7-one (0.58 g, 59%) as a brown solid.

LCMS (method B) retention time 1.24min,268 (M+H)

D) Preparation of 7-chloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine

N, N-dimethylaniline (1.95 g,15.3 mmol) was added to a single neck round bottom flask containing a mixture of 6- (3-cyclopropylphenoxy) -4H-pyrazolo [1,5-a ] pyrimidin-7-one (1.0 g,3.74 mmol) and phosphorus (V) oxychloride (26.5 mL,284 mmol) at 0 ℃. The reaction mixture was stirred at 85 ℃ for 12 hours. The progress of the reaction was monitored by LCMS. After the reaction was completed, the reaction mixture was evaporated to a minimum volume, diluted with ice water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure to obtain a crude residue. The resulting crude residue was purified by silica gel chromatography (cyclohexane/ethyl acetate) to give 7-chloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine (0.6 g, 53%)

LCMS (method B) retention time 1.52min,286 (M+H)

E) Preparation of methyl 6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine-7-carboxylate

The autoclave vessel was charged with 7-chloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine (0.2 g,0.70 mmol), triethylamine (0.2 mL,0.56 mmol), pd (dppf) Cl ₂CH₂Cl₂ (0.14 g,0.17 mmol) and methanol (20 mL). The reactor was then flushed three times with carbon monoxide and charged with carbon monoxide at a pressure of 10 bar. The reaction mixture was heated to 80 ℃ for 5 hours. The progress of the reaction was monitored by LCMS. After the reaction was completed, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure to obtain a crude residue. The resulting crude residue was purified by silica gel chromatography (cyclohexane/ethyl acetate) to give methyl 6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine-7-carboxylate (0.13 g, 60%) as a yellow solid.

LCMS (method D) retention time 1.19min,310 (M+H)

F) Preparation of lithium 6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine-7-carboxylate

To a solution of methyl 6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine-7-carboxylate (100 mg,0.32 mmol) in tetrahydrofuran (4 mL) and water (2 mL) was added lithium hydroxide (0.024 g,0.96 mmol). The reaction mass was stirred at room temperature for 1 hour. The progress of the reaction was monitored by TLC and LCMS. After the completion of the reaction, the reaction mixture was concentrated under reduced pressure to obtain lithium 6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine-7-carboxylate (95 mg, 97%) as an off-white solid, which was used as it was in the next step.

LCMS (method C) retention time 0.96min,296 (M+H)

G) Preparation of 6- (3-cyclopropylphenoxy) -N- [1- [ (2, 4-dichlorophenyl) methyl ] -2- (1, 3-dioxoisoindolin-2-yl) oxy-ethyl ] pyrazolo [1,5-a ] pyrimidine-7-carboxamide

To lithium 6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine-7-carboxylate (0.10 g,0.33 mmol) in anhydrous N, N-dimethylformamide (4 mL) was added ammonium 1- [ (2, 4-dichlorophenyl) methyl ] -2- (1, 3-dioxoisoindolin-2-yl) oxy-ethyl ]2, 2-trifluoroacetate (0.19 g,0.39 mmol) followed by HATU (0.26 g,0.66 mmol). The reaction mixture was stirred at room temperature for 12 hours. The reaction was monitored by TLC and LCMS. After completion, the reaction mixture was diluted with water to precipitate a solid from the reaction mass, filtered and washed with water and methyl tert-butyl ether and finally dried under vacuum to give 6- (3-cyclopropylphenoxy) -N- [1- [ (2, 4-dichlorophenyl) methyl ] -2- (1, 3-dioxoisoindolin-2-yl) oxy-ethyl ] pyrazolo [1,5-a ] pyrimidine-7-carboxamide (0.15 g, 66%).

LCMS (method D) retention time 1.22min,640.0 (M-H)

H) Preparation of N- [1- (aminooxymethyl) -2- (2, 4-dichlorophenyl) ethyl ] -6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine-7-carboxamide

To 6- (3-cyclopropylphenoxy) -N- [1- [ (2, 4-dichlorophenyl) methyl ] -2- (1, 3-dioxoisoindolin-2-yl) oxy-ethyl ] pyrazolo [1,5-a ] pyrimidine-7-carboxamide (100 mg,0.15 mmol) in tetrahydrofuran (6 mL) was added hydrazine monohydrate (46.7 μl,0.93 mmol). The reaction mixture was stirred at room temperature for 1 hour. A precipitate formed during the reaction. After completion, the reaction mixture was diluted with methyl tert-butyl ether and ethyl acetate (8:2, 15 ml) and filtered through a funnel. The filtrate was washed with water, dried over sodium sulfate and concentrated under reduced pressure to give N- [1- (aminooxymethyl) -2- (2, 4-dichlorophenyl) ethyl ] -6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine-7-carboxamide (80 mg, 90%) which was used directly in the next step.

LCMS (method D) retention time 1.39min,512.0 (M+H)

I) Preparation of 3- [6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidin-7-yl ] -5- [ (2, 4-dichlorophenyl) methyl ] -5, 6-dihydro-4H-1, 2, 4-oxadiazine

N- [1- (aminooxymethyl) -2- (2, 4-dichlorophenyl) ethyl ] -6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine-7-carboxamide (350 mg,0.68 mmol) was dissolved in dichloromethane (5 mL). To this solution was added phosphorus pentachloride (213 mg,1.02 mmol) and the mixture was stirred at room temperature for 1.5 hours. The reaction was monitored by TLC and LCMS. After completion, the reaction mixture was quenched with saturated sodium bicarbonate solution and diluted with water and extracted with ethyl acetate (15 ml×2). The organic layers were combined and dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting crude residue was purified by silica gel chromatography (cyclohexane/ethyl acetate) to give 3- [6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidin-7-yl ] -5- [ (2, 4-dichlorophenyl) methyl ] -5, 6-dihydro-4H-1, 2, 4-oxadiazine (55 mg, 16%).

¹ H NMR (400 MHz, acetonitrile -d3)δppm 8.32(s,1H),8.08(d,J＝2.5Hz,1H),7.35(d,J＝2.3Hz,1H),7.10-7.20(m,2H),7.06(dd,J＝8.3,2.1Hz,1H),6.77(d,J＝7.4Hz,1H),6.73(dd,J＝2.6,0.9Hz,1H),6.70-6.72(m,1H),6.68(br s,1H),5.84(br d,J＝3.4Hz,1H),3.73-3.84(m,1H),3.66-3.73(m,2H),2.78-2.91(m,2H),1.74-1.84(m,1H),0.80-0.93(m,2H),0.50-0.65(m,2H))

LCMS (method B) retention time 2.98min,494 (M+H)

Example P2 preparation of 3- [ 3-chloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidin-7-yl ] -5- [ (2, 4-dichlorophenyl) methyl ] -5, 6-dihydro-4H-1, 2, 4-oxadiazine (compound 1.2, table T1)

Note that N- [1- (aminooxymethyl) -2- (2, 4-dichlorophenyl) ethyl ] -6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine-7-carboxamide is prepared as mentioned in example 1 (steps a through h).

(Compound 1.2 of Table T1)

A) Preparation of3- [ 3-chloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidin-7-yl ] -5- [ (2, 4-dichlorophenyl) methyl ] -5, 6-dihydro-4H-1, 2, 4-oxadiazine

N- [1- (aminooxymethyl) -2- (2, 4-dichlorophenyl) ethyl ] -6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine-7-carboxamide (80 mg,0.15 mmol) was dissolved in dichloromethane (3 mL). To this solution was added phosphorus pentachloride (97.5 mg,0.46 mmol) and the mixture was stirred at room temperature for 12 hours. The reaction was monitored by TLC and LCMS. After completion, the reaction mixture was quenched with saturated sodium bicarbonate solution, diluted with water and extracted with ethyl acetate (15 ml×2). The organic layers were combined and dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting crude residue was purified by reverse phase column chromatography (70% acetonitrile/water) to give 3- [ 3-chloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidin-7-yl ] -5- [ (2, 4-dichlorophenyl) methyl ] -5, 6-dihydro-4H-1, 2, 4-oxadiazine (16 mg, 19%)

¹H NMR(400MHz,CDCl₃)δppm 8.46(s,1H),8.08(s,1H),7.38(s,1H),7.21(t,J＝7.0Hz,1H),7.08-7.16(m,2H),6.84(br d,J＝7.8Hz,1H),6.71-6.80(m,2H),5.71(br s,1H),3.84-4.00(m,3H),2.91-3.08(m,2H),1.81-1.92(m,1H),0.92-1.04(m,2H),0.61-0.77(m,2H)

LCMS (method D) retention time 1.24min,528 (M+H)

Example P3 preparation of 3- [6- (3-cyclopropylphenoxy) -2-fluoro-pyrazolo [1,5-a ] pyrimidin-7-yl ] -5- [ (2, 4-dichlorophenyl) methyl ] -5, 6-dihydro-4H-1, 2, 4-oxadiazine (compound 1.3 of Table T1)

(Compound 1.3 of Table T1)

A) Preparation of 6- (3-cyclopropylphenoxy) -2-fluoro-4H-pyrazolo [1,5-a ] pyrimidin-7-one

In a single neck round bottom flask, a mixture of ethyl 2- (3-cyclopropylphenoxy) -3- (dimethylamino) prop-2-enoate (0.5 g,1.73 mmol), 5-fluoro-1H-pyrazol-3-amine (0.17 g,1.73 mmol) and sodium acetate (0.14 g,1.73 mmol) as prepared in example 1 steps a) and b) (see above) in acetic acid (5 mL) was stirred at 100 ℃ for 16 hours. The progress of the reaction was monitored by LCMS. After the reaction was completed, the reaction mass was cooled to room temperature, diluted with ice-cold water to precipitate an off-white solid, which was filtered on a buchner funnel, washed with cold water and dried to give 6- (3-cyclopropylphenoxy) -2-fluoro-4H-pyrazolo [1,5-a ] pyrimidin-7-one (0.45 g, 82%) as an off-white solid.

LCMS (method B) retention time 1.32min 284 (M-H)

B) Preparation of 7-chloro-6- (3-cyclopropylphenoxy) -2-fluoro-pyrazolo [1,5-a ] pyrimidine

To a mixture of 6- (3-cyclopropylphenoxy) -2-fluoro-4H-pyrazolo [1,5-a ] pyrimidin-7-one (1.5 g,5.25 mmol) and phosphorus (V) oxychloride (37.3 mL,399 mmol) was added pyridine (1.71 mL,21.0 mmol) in a single neck round bottom flask at 0 ℃. The reaction mixture was stirred at 85 ℃ for 12 hours. The progress of the reaction was monitored by LCMS. After the reaction was completed, the reaction mixture was concentrated to a minimum volume and diluted with ice water. The desired material was extracted with ethyl acetate, and the organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure to obtain a crude residue. The resulting crude residue was purified by silica gel chromatography (cyclohexane/ethyl acetate) to give 7-chloro-6- (3-cyclopropylphenoxy) -2-fluoro-pyrazolo [1,5-a ] pyrimidine (0.9 g, 53%) as a pale yellow solid.

LCMS (method B) retention time 1.70min,304 (M+H)

C) Preparation of methyl 6- (3-cyclopropylphenoxy) -2-fluoro-pyrazolo [1,5-a ] pyrimidine-7-carboxylate

The autoclave vessel was charged with 7-chloro-6- (3-cyclopropylphenoxy) -2-fluoro-pyrazolo [1,5-a ] pyrimidine (0.7 g,2.30 mmol), triethylamine (0.65 mL,4.61 mmol), pd (dppf) Cl _2.CH₂Cl₂ (0.47 g,0.57 mmol) in methanol (69.1 mL). The reactor was flushed three times with carbon monoxide gas and then charged with carbon monoxide at a pressure of 10 bar. The reaction mixture was heated to 80 ℃ for 3 hours. The progress of the reaction was monitored by LCMS. After the reaction was completed, the reaction mixture was diluted with water, and the desired material was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and concentrated under reduced pressure to give a crude residue which was purified by silica gel chromatography (cyclohexane/ethyl acetate) to give methyl 6- (3-cyclopropylphenoxy) -2-fluoro-pyrazolo [1,5-a ] pyrimidine-7-carboxylate (0.40 g, 50%) as a yellow viscous material.

LCMS (method B) retention time 1.65min,328 (M+H)

D) Preparation of lithium 6- (3-cyclopropylphenoxy) -2-fluoro-pyrazolo [1,5-a ] pyrimidine-7-carboxylate

To a solution of methyl 6- (3-cyclopropylphenoxy) -2-fluoro-pyrazolo [1,5-a ] pyrimidine-7-carboxylate (250 mg,0.76 mmol) in tetrahydrofuran (3 mL) and water (1 mL) was added lithium hydroxide (57.7 mg,2.29 mmol). The reaction mass was stirred at room temperature for 2 hours. The progress of the reaction was monitored by TLC and LCMS. After the completion of the reaction, the reaction mixture was concentrated under reduced pressure, followed by co-distillation with toluene (10 mL) twice to obtain lithium 6- (3-cyclopropylphenoxy) -2-fluoro-pyrazolo [1,5-a ] pyrimidine-7-carboxylate (225 mg, 92%) as a solid, which was used directly in the next step.

LCMS (method B) retention time 1.47min,314 (M+H)

E) Preparation of 6- (3-cyclopropylphenoxy) -N- [1- [ (2, 4-dichlorophenyl) methyl ] -2- (1, 3-dioxoisoindolin-2-yl) oxy-ethyl ] -2-fluoro-pyrazolo [1,5-a ] pyrimidine-7-carboxamide

To lithium 6- (3-cyclopropylphenoxy) -2-fluoro-pyrazolo [1,5-a ] pyrimidine-7-carboxylate (225 mg,0.70 mmol) in anhydrous N, N-dimethylformamide (4.5 mL) was added ammonium [1- [ (2, 4-dichlorophenyl) methyl ] -2- (1, 3-dioxoisoindolin-2-yl) oxy-ethyl ]2, 2-trifluoroacetate (405 mg,0.84 mmol), followed by 1- [ bis (dimethylamino) methylene ] -1H-1,2, 3-triazolo [4,5-b ] pyridinium 3-oxide Hexafluorophosphate (HATU) (0.56 g,1.41 mmol). The reaction mixture was stirred at room temperature for 12 hours. The reaction was monitored by TLC and LCMS. After completion, the reaction mixture was diluted with water to precipitate solids from the reaction mass. The precipitate was filtered off, washed with water and methyl tert-butyl ether and dried under vacuum to give 6- (3-cyclopropylphenoxy) -N- [1- [ (2, 4-dichlorophenyl) methyl ] -2- (1, 3-dioxoisoindolin-2-yl) oxy-ethyl ] -2-fluoro-pyrazolo [1,5-a ] pyrimidine-7-carboxamide (0.37 g, 75%) as a white solid.

LCMS (method D) retention time 1.28min,660 (M+H)

F) Preparation of N- [1- (aminooxymethyl) -2- (2, 4-dichlorophenyl) ethyl ] -6- (3-cyclopropylphenoxy) -2-fluoro-pyrazolo [1,5-a ] pyrimidine-7-carboxamide

To 6- (3-cyclopropylphenoxy) -N- [1- [ (2, 4-dichlorophenyl) methyl ] -2- (1, 3-dioxoisoindolin-2-yl) oxy-ethyl ] -2-fluoro-pyrazolo [1,5-a ] pyrimidine-7-carboxamide (200 mg,0.30 mmol) in tetrahydrofuran (6 mL) was added hydrazine monohydrate (90.8 μl,1.81 mmol). The reaction mixture was stirred at room temperature for 2 hours. The progress of the reaction was monitored by TLC and LCMS. After completion, the solid precipitated and was filtered through a buchner funnel. The filtrate was diluted with ethyl acetate (15 mL) and washed with water, dried over sodium sulfate and concentrated under reduced pressure to give N- [1- (aminooxymethyl) -2- (2, 4-dichlorophenyl) ethyl ] -6- (3-cyclopropylphenoxy) -2-fluoro-pyrazolo [1,5-a ] pyrimidine-7-carboxamide (150 mg, 84%) which was used directly in the next step.

LCMS (method xy/QDA) retention time 1.31min,530 (M+H)

G) Preparation of 3- [6- (3-cyclopropylphenoxy) -2-fluoro-pyrazolo [1,5-a ] pyrimidin-7-yl ] -5- [ (2, 4-dichlorophenyl) methyl ] -5, 6-dihydro-4H-1, 2, 4-oxadiazine

N- [1- (aminooxymethyl) -2- (2, 4-dichlorophenyl) ethyl ] -6- (3-cyclopropylphenoxy) -2-fluoro-pyrazolo [1,5-a ] pyrimidine-7-carboxamide (0.15 g,0.28 mmol) was dissolved in dichloromethane (4.5 mL), phosphorus pentachloride (88.3 mg,0.42 mmol) was added and the mixture was stirred at room temperature for 2 hours. The reaction was monitored by TLC and LCMS. The reaction mixture was then quenched with saturated sodium bicarbonate solution, diluted with water and extracted twice with ethyl acetate (30 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting crude residue was purified by reverse phase chromatography (water/acetonitrile) to give 3- [6- (3-cyclopropylphenoxy) -2-fluoro-pyrazolo [1,5-a ] pyrimidin-7-yl ] -5- [ (2, 4-dichlorophenyl) methyl ] -5, 6-dihydro-4H-1, 2, 4-oxadiazine (26 mg, 18%).

¹H NMR(400MHz,CDCl₃)δppm 8.45(s,1H),7.40(d,J＝1.83Hz,1H),7.15-7.25(m,3H),6.85(d,J＝7.95Hz,1H),6.73-6.80(m,2

H),6.33(d,J＝5.14Hz,1H),5.55(br d,J＝3.18Hz,1H),3.88-3.99(m,3H),2.95-3.08(m,2H),1.84-1.92(m,1H),0.97-1.03(m,2H),0.66-0.76(m,2H)

LCMS (method B) retention time 1.80min,512 (M+H)

Example P4 preparation of 3- [ 2-chloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidin-7-yl ] -5- [ (2, 4-dichlorophenyl) methyl ] -5, 6-dihydro-4H-1, 2, 4-oxadiazine (compound 1.4 of Table T1)

(Compound 1.4 of Table T1)

A) Preparation of 2-chloro-6- (3-cyclopropylphenoxy) -4H-pyrazolo [1,5-a ] pyrimidin-7-one

In a single neck round bottom flask, a mixture of ethyl 2- (3-cyclopropylphenoxy) -3- (dimethylamino) prop-2-enoate (0.5 g,2.00 mmol), 3-chloro-1H-pyrazol-5-amine (0.2 g,2.00 mmol) and sodium acetate (0.2 g,2.00 mmol) as prepared in example 1 steps a) and b) (see above) in acetic acid (10 mL) was stirred at 110 ℃ for 4 hours. The progress of the reaction was monitored by LCMS. After the reaction was completed, the reaction mass was cooled to room temperature, diluted with ice-cold water to precipitate an off-white solid, which was filtered on a buchner funnel, washed with cold water and dried to give 2-chloro-6- (3-cyclopropylphenoxy) -4H-pyrazolo [1,5-a ] pyrimidin-7-one (0.49 g, 90%) as an off-white solid.

LCMS (method B) retention time 1.38min,302 (M+H)

B) Preparation of 2, 7-dichloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine

To a mixture of 2-chloro-6- (3-cyclopropylphenoxy) -4H-pyrazolo [1,5-a ] pyrimidin-7-one (0.2 g,0.66 mmol) and phosphorus (V) oxychloride (4.70 mL,50.4 mmol) was added pyridine (0.21 mL,2.65 mmol) in a single neck round bottom flask at 0 ℃. The reaction mixture was stirred at 90 ℃ for 4 hours. The progress of the reaction was monitored by LCMS. After the reaction was completed, the reaction mixture was concentrated to a minimum volume and diluted with ice water. The desired material was extracted with ethyl acetate, and the organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure to obtain a crude residue. The resulting crude residue was purified by silica gel chromatography (cyclohexane/ethyl acetate) to give 2, 7-dichloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine (0.22 g, 74%) as a yellow solid.

LCMS (method B) retention time 1.77min,320 (M+H)

C) Preparation of methyl 2-chloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine-7-carboxylate

The autoclave vessel was charged with 2, 7-dichloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine (0.5 g,1.56 mmol), triethylamine (0.44 mL,3.12 mmol), pd (dppf) Cl _2.CH₂Cl₂ (0.32 g,0.39 mmol) in methanol (20 mL). The reactor was flushed three times with carbon monoxide and then charged with carbon monoxide at a pressure of 10 bar. The reaction mixture was heated to 80 ℃ for 2 hours. The progress of the reaction was monitored by LCMS. After the reaction was completed, the reaction mixture was diluted with water, and the desired material was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and concentrated under reduced pressure to give a crude residue which was purified by silica gel chromatography (cyclohexane/ethyl acetate 0-50%) to give methyl 2-chloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine-7-carboxylate (0.38 g, 71%) as a yellow viscous material.

LCMS (method B) retention time 1.70min,344 (M+H)

D) Preparation of lithium 2-chloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine-7-carboxylate

To a solution of methyl 2-chloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine-7-carboxylate (260 mg,0.76 mmol) in tetrahydrofuran (1 mL) and water (0.5 mL) was added lithium hydroxide (97.1 mg,2.27 mmol). The reaction mass was stirred at room temperature for 6 hours. The progress of the reaction was monitored by TLC and LCMS. After the completion of the reaction, the reaction mixture was concentrated under reduced pressure, followed by continuous co-distillation with toluene (2×10 mL) twice to obtain lithium 2-chloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine-7-carboxylate (362 mg, 96%) as a solid, which was directly used in the next step.

LCMS (method B) retention time 1.57min,330 (M+H)

E) Preparation of 2-chloro-6- (3-cyclopropylphenoxy) -N- [1- [ (2, 4-dichlorophenyl) methyl ] -2- (1, 3-dioxoisoindolin-2-yl) oxy-ethyl ] pyrazolo [1,5-a ] pyrimidine-7-carboxamide

To lithium 2-chloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine-7-carboxylate (0.35 g,0.73 mmol) in anhydrous N, N-dimethylformamide (2.19 mL) was added ammonium [1- [ (2, 4-dichlorophenyl) methyl ] -2- (1, 3-dioxoisoindolin-2-yl) oxy-ethyl ]2, 2-trifluoroacetate (0.41 g,0.87 mmol), followed by 1- [ bis (dimethylamino) methylene ] -1H-1,2, 3-triazolo [4,5-b ] pyridinium 3-oxide Hexafluorophosphate (HATU) (0.33 g,0.87 mmol). The reaction mixture was stirred at room temperature for 1 hour. The reaction was monitored by TLC and LCMS. After the reaction was completed, the reaction mixture was diluted with water to precipitate solids from the reaction mass. The precipitate was filtered off, washed with water and methyl tert-butyl ether and dried under vacuum to give 2-chloro-6- (3-cyclopropylphenoxy) -N- [1- [ (2, 4-dichlorophenyl) methyl ] -2- (1, 3-dioxoisoindolin-2-yl) oxy-ethyl ] pyrazolo [1,5-a ] pyrimidine-7-carboxamide (0.5 g, 81%) as a yellow solid.

LCMS (method B) retention time 1.91min,676 (M+H)

F) Preparation of N- [1- (aminooxymethyl) -2- (2, 4-dichlorophenyl) ethyl ] -2-chloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine-7-carboxamide

To 2-chloro-6- (3-cyclopropylphenoxy) -N- [1- [ (2, 4-dichlorophenyl) methyl ] -2- (1, 3-dioxoisoindolin-2-yl) oxy-ethyl ] pyrazolo [1,5-a ] pyrimidine-7-carboxamide (100 mg,0.14 mmol) in tetrahydrofuran (2 mL) was added hydrazine monohydrate (11 μl,0.22 mmol). The reaction mixture was stirred at room temperature for 2 hours. The progress of the reaction was monitored by TLC and LCMS. After completion, the solid precipitated and was filtered through a buchner funnel. The filtrate was diluted in ethyl acetate (15 mL) and washed with water, dried over sodium sulfate and concentrated under reduced pressure to give N- [1- (aminooxymethyl) -2- (2, 4-dichlorophenyl) ethyl ] -2-chloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine-7-carboxamide (80 mg, 79%) which was used directly in the next step.

LCMS (method B) retention time 1.69min,546 (M+H)

G) Preparation of3- [ 2-chloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidin-7-yl ] -5- [ (2, 4-dichlorophenyl) methyl ] -5, 6-dihydro-4H-1, 2, 4-oxadiazine

N- [1- (aminooxymethyl) -2- (2, 4-dichlorophenyl) ethyl ] -2-chloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidine-7-carboxamide (80.0 mg,0.15 mmol) was dissolved in dichloromethane (5 mL), phosphorus pentachloride (46 mg,0.22 mmol) was added and the mixture was stirred at room temperature for 1 hour. The reaction was monitored by TLC and LCMS. The reaction mixture was then quenched with saturated sodium bicarbonate solution, then diluted with water and extracted twice with ethyl acetate (30 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting crude residue was purified by reverse phase chromatography (water/acetonitrile) to give 3- [ 2-chloro-6- (3-cyclopropylphenoxy) pyrazolo [1,5-a ] pyrimidin-7-yl ] -5- [ (2, 4-dichlorophenyl) methyl ] -5, 6-dihydro-4H-1, 2, 4-oxadiazine (15 mg, 77%).

¹H NMR(400MHz,CDCl₃)δppm 8.43(s,1H),7.39(d,J＝2.08Hz,1H),7.24-7.30(m,2H),7.16-7.23(m,2H),6.83(d,J＝7.70Hz,1H),6.76(d,J＝2.57Hz,1H),6.73(s,1H),5.68(br d,J＝3.42Hz,1H),3.95(m,3H),2.95-3.09(m,2H),1.82-1.94(m,1H),0.93-1.02(m,2H),0.65-0.73(m,2H)

LCMS (method B) retention time 1.85min,528 (M+H)

Example P5 preparation of 3- [7- (3-cyclopropylphenoxy) imidazo [1,2-b ] pyridazin-8-yl ] -5- [ (2, 4-dichlorophenyl) methyl ] -5, 6-dihydro-4H-1, 2, 4-oxadiazine (Compound 1.5 of Table T1)

(Compound 1.5 of Table T1)

A) Preparation of 2- [ (2-bromoimidazol-1-yl) methoxy ] ethyl-trimethyl-silane

To a solution of 2-bromo-1H-imidazole (2.0 g,14 mmol) in tetrahydrofuran (5 mL) was added sodium hydride (0.65 g,16mmol,60 mass%) at 0 ℃ and the reaction mixture was stirred for 30 min. 2- (trimethylsilyl) ethoxymethyl chloride (2.8 mL,15 mmol) was then added at 0℃and the resulting reaction mixture was stirred at room temperature for 2 hours. The reaction was monitored by TLC and LCMS. After completion, the reaction mixture was diluted with water, extracted with ethyl acetate, and the organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting crude residue was purified by silica gel chromatography (cyclohexane/ethyl acetate) to give 2- [ (2-bromoimidazol-1-yl) methoxy ] ethyl-trimethyl-silane (2.6 g, 69%) as a pale yellow liquid.

¹H NMR(400MHz,CDCl₃)δppm 7.11(d,J＝1.63Hz,1H),7.05(d,J＝1.38Hz,1H),5.27(s,2H),3.53(dd,J＝8.69,7.69Hz,2H),0.87-0.99(m,2H),-0.02(s,9H)

B) Preparation of 2- (3-cyclopropylphenoxy) -1- [1- (2-trimethylsilylethoxymethyl) imidazol-2-yl ] ketene

In a two-necked round bottom flask, 2- [ (2-bromoimidazol-1-yl) methoxy ] ethyl-trimethyl-silane (2.35 g.,8.50 mmol) was dissolved in tetrahydrofuran (42 mL) and cooled to 0 ℃. To this was added dropwise a solution of isopropyl magnesium chloride-lithium chloride complex (1.3 mol/L) in THF (6.5 mL,8.50 mmol) and stirred for 30 minutes. After this, 2- (3-cyclopropylphenoxy) -N-methoxy-N-methyl-acetamide (prepared separately in three steps as described below) (1.0 g,4.25 mmol) was dissolved in tetrahydrofuran. The reaction mixture was stirred at room temperature for 1 hour. The reaction was monitored by TLC and LCMS. After the reaction was completed, the reaction mixture was quenched with saturated ammonium chloride solution, diluted with water, and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The resulting crude residue was purified by silica gel chromatography (cyclohexane/ethyl acetate) to give 2- (3-cyclopropylphenoxy) -1- [1- (2-trimethylsilylethoxymethyl) imidazol-2-yl ] ketene (1.63 g, 92%) as a pale yellow liquid.

LCMS (method B) retention time 1.69min 373 (M+H)

C) Preparation of 2- (3-cyclopropylphenoxy) -1- (1H-imidazol-2-yl) ethanone

In a round bottom flask, 2- (3-cyclopropylphenoxy) -1- [1- (2-trimethylsilylethoxymethyl) imidazol-2-yl ] ethanone (0.25 g,0.47 mmol) was dissolved in methanol (2 mL) and hydrochloric acid (1.4 mL,5.63 mmol) was added thereto. The reaction mixture was stirred at 80 ℃ for 3 hours. The progress of the reaction was monitored by TLC and LCMS. After completion, the reaction mixture was concentrated under reduced pressure, diluted with water and extracted with ethyl acetate. The organic layer was washed with sodium bicarbonate. The combined organic layers were dried under reduced pressure to give crude 2- (3-cyclopropylphenoxy) -1- (1H-imidazol-2-yl) ethanone (0.06 g, 50%) which was used as such in the next step.

LCMS (method C) retention time 1.03min,243 (M+H)

D) Preparation of 2- (3-cyclopropylphenoxy) -3- (dimethylamino) -1- (1H-imidazol-2-yl) prop-2-en-1-one

2- (3-Cyclopropylphenoxy) -1- (1H-imidazol-2-yl) ethanone (0.60 g,2.0 mmol) and 1-tert-butoxy-N, N, N ', N' -tetramethyl-methyldiamine (5.0 g,20.0 mmol) were heated to 90℃in a sealed glass reactor for 2 hours. The progress of the reaction was monitored by LCMS. After completion, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure to obtain a crude residue. The resulting crude residue was purified by silica gel chromatography (cyclohexane/ethyl acetate) to give 2- (3-cyclopropylphenoxy) -3- (dimethylamino) -1- (1H-imidazol-2-yl) prop-2-en-1-one (0.3 g, 40%).

LCMS (method B) retention time 1.05min,298 (M+H)

E) Preparation of 7- (3-cyclopropylphenoxy) -5H-imidazo [1,2-b ] pyridazin-8-one

2- (3-Cyclopropylphenoxy) -3- (dimethylamino) -1- (1H-imidazol-2-yl) prop-2-en-1-one (0.03 g,0.10 mmol) was dissolved in N-methyl-2-pyrrolidone (1 mL) in a round bottom flask, and potassium tert-butoxide (0.012 g,0.10 mmol) was added thereto as a solution in N-methyl-2-pyrrolidone (0.5 mL). The resulting reaction mixture was stirred at room temperature for 30 minutes. To this was added a solution of 4-nitrobenzoic acid amino ester (0.022 g,0.12 mmol) in N-methyl-2-pyrrolidone (1 mL), and the reaction mixture was stirred at room temperature for 16 hours. The progress of the reaction was monitored by LCMS. After completion, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure to obtain a crude residue. The resulting crude residue was purified by silica gel chromatography (cyclohexane/ethyl acetate) to give a mixture of 1- (1-aminoimidazol-2-yl) -2- (3-cyclopropylphenoxy) -3- (dimethylamino) prop-2-en-1-one and 7- (3-cyclopropylphenoxy) -5H-imidazo [1,2-b ] pyridazin-8-one (60 mg). The mixture was used as such for the next step.

LCMS (method B) retention times of 0.28min,313 (M+H) and 1.9min,268 (M+H)

F) Preparation of 8-chloro-7- (3-cyclopropylphenoxy) imidazo [1,2-b ] pyridazine

A mixture of 1- (1-aminoimidazol-2-yl) -2- (3-cyclopropylphenoxy) -3- (dimethylamino) prop-2-en-1-one and 7- (3-cyclopropylphenoxy) -5H-imidazo [1,2-b ] pyridazin-8-one (0.4 g), N-dimethylaniline (0.7 mL,5 mmol) and phosphorus (V) oxychloride (8 mL,90 mmol) was stirred at 90℃for 12 hours. The progress of the reaction was monitored by LCMS. After completion, the reaction mixture was diluted with ice water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure to obtain a crude residue. The resulting crude residue was purified by silica gel chromatography (cyclohexane/ethyl acetate) to give 8-chloro-7- (3-cyclopropylphenoxy) imidazo [1,2-b ] pyridazine (0.3 g, 30%) as a brown viscous material.

LCMS (method B) retention time 1.47min,286 (M+H)

G) Preparation of methyl 7- (3-cyclopropylphenoxy) imidazo [1,2-b ] pyridazine-8-carboxylate

The autoclave vessel was charged with 8-chloro-7- (3-cyclopropylphenoxy) imidazo [1,2-b ] pyridazine (0.13 g,0.45 mmol), triethylamine (0.13 mL,0.91 mmol), pd (dppf) Cl ₂.CH₂Cl₂ (0.093 g,0.11 mmol) in methanol (20 mL), and the reactor was flushed three times with carbon monoxide and charged with carbon monoxide at a pressure of 10 bar. The reaction mixture was heated to 80 ℃ for 5 hours. The progress of the reaction was monitored by LCMS. After the reaction was completed, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure to obtain a crude residue. The resulting crude residue was purified by silica gel chromatography (cyclohexane/ethyl acetate) to give methyl 7- (3-cyclopropylphenoxy) imidazo [1,2-b ] pyridazine-8-carboxylate (0.075 g, 53%) as a yellow solid.

LCMS (method B) retention time 2.03min,310 (M+H)

H) Preparation of lithium 7- (3-cyclopropylphenoxy) imidazo [1,2-b ] pyridazine-8-carboxylate

To a solution of methyl 7- (3-cyclopropylphenoxy) imidazo [1,2-b ] pyridazine-8-carboxylate (0.05 g,0.16 mmol) in tetrahydrofuran (1 mL) and water (0.05 mL) was added lithium hydroxide monohydrate (20 mg,0.48 mmol). The reaction mass was stirred at room temperature for 16 hours. The progress of the reaction was monitored by TLC and LCMS. After completion, the reaction mixture was concentrated under reduced pressure at 30 ℃, followed by continuous co-distillation with toluene (2×10 mL) twice to give lithium 7- (3-cyclopropylphenoxy) imidazo [1,2-b ] pyridazine-8-carboxylate (50 mg crude product), which was used as such in the next step.

LCMS (method B) retention time 0.51min,296 (M+H)

I) Preparation of 7- (3-cyclopropylphenoxy) -N- [1- [ (2, 4-dichlorophenyl) methyl ] -2- (1, 3-dioxoisoindolin-2-yl) oxy-ethyl ] imidazo [1,2-b ] pyridazine-8-carboxamide

To lithium 7- (3-cyclopropylphenoxy) imidazo [1,2-b ] pyridazine-8-carboxylate (0.24 g,0.71 mmol) in anhydrous N, N-dimethylformamide (2.14 mL) was added ammonium [1- [ (2, 4-dichlorophenyl) methyl ] -2- (1, 3-dioxoisoindolin-2-yl) oxy-ethyl ]2, 2-trifluoroacetate (0.41 g,0.86 mmol), followed by 1- [ bis (dimethylamino) methylene ] -1H-1,2, 3-triazolo [4,5-b ] pyridinium 3-oxide Hexafluorophosphate (HATU) (0.32 g,0.86 mmol). The reaction mixture was stirred at room temperature for 1 hour. The progress of the reaction was monitored by TLC and LCMS. After the reaction was completed, the reaction mixture was diluted with water to precipitate solids from the reaction mass. The precipitate was filtered off and washed with water and methyl tert-butyl ether and dried under vacuum to give 7- (3-cyclopropylphenoxy) -N- [1- [ (2, 4-dichlorophenyl) methyl ] -2- (1, 3-dioxoisoindolin-2-yl) oxy-ethyl ] imidazo [1,2-b ] pyridazine-8-carboxamide (0.47 g, 82%) as an off-white solid.

LCMS (method B) retention time 1.68min,642 (M+H)

J) Preparation of N- [1- (aminooxymethyl) -2- (2, 4-dichlorophenyl) ethyl ] -7- (3-cyclopropylphenoxy) imidazo [1,2-b ] pyridazine-8-carboxamide

To 7- (3-cyclopropylphenoxy) -N- [1- [ (2, 4-dichlorophenyl) methyl ] -2- (1, 3-dioxoisoindolin-2-yl) oxy-ethyl ] imidazo [1,2-b ] pyridazine-8-carboxamide (460 mg,0.71 mmol) in tetrahydrofuran (2 mL) was added hydrazine monohydrate (52.7 μl,0.22 mmol). The reaction mixture was stirred at room temperature for 2 hours. The progress of the reaction was monitored by TLC and LCMS. After completion, the solid precipitated and was filtered through a buchner funnel. The filtrate was diluted in ethyl acetate (15 mL) and washed with water, dried over sodium sulfate and concentrated under reduced pressure to give N- [1- (aminooxymethyl) -2- (2, 4-dichlorophenyl) ethyl ] -7- (3-cyclopropylphenoxy) imidazo [1,2-b ] pyridazine-8-carboxamide (370 mg, 91%) which was used directly in the next step.

LCMS (method B) retention time 1.37min,512 (M+H)

K) Preparation of 3- [7- (3-cyclopropylphenoxy) imidazo [1,2-b ] pyridazin-8-yl ] -5- [ (2, 4-dichlorophenyl) methyl ] -5, 6-dihydro-4H-1, 2, 4-oxadiazine

N- [1- (aminooxymethyl) -2- (2, 4-dichlorophenyl) ethyl ] -7- (3-cyclopropylphenoxy) imidazo [1,2-b ] pyridazine-8-carboxamide (190 mg,0.37 mmol) was dissolved in dichloromethane (5 mL), phosphorus pentachloride (116 mg,0.55 mmol) was added and the mixture was stirred at room temperature for 1 hour. The progress of the reaction was monitored by TLC and LCMS. After completion, the reaction mixture was then quenched with saturated sodium bicarbonate solution, and diluted with water and extracted twice with ethyl acetate (30 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting crude residue was purified by reverse phase chromatography (water/acetonitrile) to give 3- [7- (3-cyclopropylphenoxy) imidazo [1,2-b ] pyridazin-8-yl ] -5- [ (2, 4-dichlorophenyl) methyl ] -5, 6-dihydro-4H-1, 2, 4-oxadiazine (27 mg, 14%)

¹H NMR(400MHz,CDCl₃)δppm 8.14(s,1H),7.89(d,J＝1.38Hz,1H),7.65(d,J＝1.25Hz,1H),7.50(br s,1H),7.40(d,J＝2.00Hz,1H),7.21-7.25(m,2H),7.17(d,J＝2.13Hz,1H),6.87(d,J＝7.75Hz,1H),6.78(br d,J＝1.63Hz,2H),3.91-4.04(m,2H),3.77-3.89(m,1H),3.00-3.10(m,2H),1.85-1.90(m,1H),0.94-0.98(m,2H),0.66-0.74(m,2H)

LCMS (method B) retention time 1.48min,494 (M+H)

Example P6 preparation of 2- (3-cyclopropylphenoxy) -N-methoxy-N-methyl-acetamide

Step 1 preparation of methyl 2- (3-cyclopropylphenoxy) acetate

Cesium carbonate (2.76 g,8.50 mmol) was added to 3-cyclopropylphenol (1.0 g,7.08 mmol) in acetonitrile (10 mL) in a single neck round bottom flask. To this reaction mixture was added methyl 2-bromoacetate (1.29 g,8.50 mmol) and the resulting reaction mixture was stirred at room temperature for 12h. The progress of the reaction was monitored by LCMS. After the reaction was completed, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and concentrated under reduced pressure to obtain a crude residue, the crude residue was purified by silica gel chromatography (cyclohexane/ethyl acetate) to give methyl 2- (3-cyclopropylphenoxy) acetate (1.6 g, 98%).

LCMS (method B) retention time 1.41min,207 (M+H)

Step 2 preparation of 2- (3-cyclopropylphenoxy) acetic acid

To a solution of methyl 2- (3-cyclopropylphenoxy) acetate (1.48 g,6.46 mmol) in tetrahydrofuran (9 mL) and water (4.5 mL) was added lithium hydroxide (0.83 g,19.40 mmol). The reaction mass was stirred at room temperature for 1 hour. The progress of the reaction was monitored by TLC and LCMS. After the reaction was completed, the mixture was diluted with water and washed with ethyl acetate. The aqueous layer was then acidified with 2N HCl and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo to give 2- (3-cyclopropylphenoxy) acetic acid (1.30 g, 99%) as a beige solid.

¹H NMR(400MHz,CDCl₃)δppm 7.19(t,J＝7.73Hz,1H),6.76(d,J＝7.63Hz,1H),6.64-6.73(m,2H),4.68(s,2H),1.84-1.92(m,1H),0.92 -1.02(m,2H),0.64-0.76(m,2H).

LCMS (method B) retention time 1.24min,190.8 (M-H)

Step 3 preparation of 2- (3-cyclopropylphenoxy) -N-methoxy-N-methyl-acetamide

To 2- (3-cyclopropylphenoxy) acetic acid (1.34 g,6.62 mmol) in ethyl acetate (27 mL) was added methoxy (methyl) ammonium chloride (0.97 g,9.93 mmol), followed by 1-propanephosphonic anhydride solution (T3P, 50% in ethyl acetate, 4.64g,7.29 mmol) and N, N-diisopropylethylamine (2.59 g,19.9 mmol). The reaction mixture was stirred at room temperature for 12 hours. The progress of the reaction was monitored by TLC and LCMS. After completion, the reaction mixture was diluted with ethyl acetate and poured into water, and the desired material was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The resulting crude residue was purified by silica gel chromatography (ethyl acetate/cyclohexane) to give 2- (3-cyclopropylphenoxy) -N-methoxy-N-methyl-acetamide (1.26 g, 76%) as a viscous material.

¹H NMR(400MHz,CDCl₃)δppm 7.16(t,J＝7.74Hz,1H),6.69-6.73(m,3H),4.79(s,2H),3.76(s,3H),3.25(s,3H),1.82-1.92(m,1H),1.67-1.67(m,1H),0.88-1.02(m,2H),0.65-0.74(m,2H).

LCMS (method B) retention time 1.32min,236 (M+H)

TABLE T1 physical data for compounds of formula (I)

Biological examples and test methods

General description of the test methods

Leaf discs or segments of different plant species are cut from plants grown in the greenhouse. Cut leaf discs or leaves Duan Zhiyu were plated on water agar in multiwell plates (24 well format). Leaf discs were sprayed with the test solution either before (prophylactic) or after (therapeutic) inoculation. The compounds to be tested were prepared as DMSO solutions (max 10 mg/mL) and diluted to the appropriate concentration with 0.025% Tween20 just before spraying. Inoculated leaf discs or leaf segments are incubated under defined conditions (temperature, relative humidity, light, etc.) according to the corresponding test system. Depending on the disease system, a single assessment of disease levels was made 3 to 14 days post inoculation. The percent disease control relative to untreated test leaf discs or segments is then calculated.

The mycelium fragments or conidium suspensions of the fungi (prepared freshly from liquid cultures of the fungi or from frozen stock) are mixed directly into the nutrient broth. A DMSO solution of the test compound (max 10 mg/mL) was diluted 50-fold with 0.025% Tween20 and 10. Mu.L of this solution was pipetted into a microtiter plate (96 well format). A nutrient broth containing fungal spore/mycelium fragments was then added to it to give the final concentration of test compound. The test plates were incubated in the dark at 24 ℃ and 96% relative humidity. Inhibition of fungal growth was determined photometrically after 2 to 7 days depending on the disease system and the percentage of antifungal activity was calculated relative to untreated test.

Example B1 Alternaria solani (ALTERNARIA SOLANI) (tomato early blight)

Tomato leaf disc cultivar beratio (Baby) was placed on agar in multiwell plates (24-well format) and sprayed with formulated test compound diluted in water. 2 days after application, leaf discs were inoculated with a spore suspension of the fungus. Inoculated leaf discs were incubated in a climatic chamber under a 12/12h (light/dark) light regimen at 23/21 ℃ (day/night) and 80% rh, and the activity of the compounds was assessed as percent disease control compared to untreated when appropriate levels of disease damage occurred on untreated test leaf discs (5-7 days post-application).

The following compounds from Table T1 gave at least 80% control of Alternaria solani at 200ppm, 1.1 when compared to untreated controls showing extensive disease development under the same conditions

EXAMPLE B2 Botrytis Fusarium (Botryotiniafuckeliana) (also known as Botrytis cinerea) (Botrytis cinerea)

Fungal conidia from frozen storage are directly mixed into a nutrient broth (Vogels) broth. After placing the (DMSO) solution of the test compound in a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. These test plates were incubated at 24 ℃ and inhibition of growth was determined photometrically 3-4 days after application.

The following compounds from Table T1 gave at least 80% control of Botrytis cinerea at 20ppm, 1.1, 1.2, 1.3, 1.4, 1.5 when compared with untreated controls showing extensive disease development under the same conditions

Example B3 Confucius cucurbita (Glomerella lagenarium) (also known as melon anthracnose (Colletotrichum lagenarium)) (cucurbit anthracnose)

Fungal conidia from frozen storage are directly mixed into the nutrient broth (PDB-potato dextrose broth). After placing the (DMSO) solution of the test compound in a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. These test plates were incubated at 24 ℃ and inhibition of growth was measured photometrically 3-4 days after application.

The following compounds from Table T1 gave at least 80% control of Consumer fungus at 20ppm 1.1, 1.5 when compared to untreated controls showing extensive disease development under the same conditions

Example B4 Fusarium nivale (Monographella nivalis) (also known as Xueyu leaf blight (Microdochium nivale), fusarium nivale) (snow mold, cereal root rot):

fungal conidia from frozen storage are directly mixed into the nutrient broth (PDB-potato dextrose broth). After placing the (DMSO) solution of the test compound in a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. These test plates were incubated at 24 ℃ and inhibition of growth was determined photometrically 4-5 days after application.

The following compounds from Table T1 gave at least 80% control of C.snow rot at 20ppm, 1.5, when compared with untreated controls showing extensive disease development under the same conditions

EXAMPLE B5 Nuclear bacteria (Pyrenophora teres) (barley net blotch (Net blotchof barley))

Barley leaf segment cultivar haloso (Hasso) was placed on agar in multiwell plates (24 well format) and sprayed with formulated test compound diluted in water. 2 days after application, the leaf segments were inoculated with a spore suspension of the fungus. Inoculated leaf sections were incubated in a climatic chamber under a12 h light/12 h dark light regimen at 20 ℃ and 65% rh, and the activity of the compounds was assessed as disease control compared to untreated when appropriate levels of disease damage occurred on untreated test leaf sections (5-7 days after application).

The following compounds from Table T1 gave at least 80% control of Rhizoctonia at 200ppm when compared with untreated controls showing extensive disease development under the same conditions 1.1

Example B6 sclerotinia sclerotiorum (rape cotton rot)

The mycelium fragments of the newly grown liquid culture of the fungus were directly mixed into the nutrient broth (PDB (potato dextrose broth)). After placing the (DMSO) solution of test compound in a microtiter plate (96-well format), the nutrient broth containing the fungal material is added. These test plates were incubated at 24 ℃ and inhibition of growth was determined photometrically 3-4 days after application.

The following compounds from Table T1 gave at least 80% control of sclerotinia at 20ppm, 1.1, 1.5 when compared to untreated controls showing extensive disease development under the same conditions

Example B7 exemplary Mycosphaerella graminearum (Septoria tritici) (leaf blight):

The following compounds from table T1 gave at least 80% control of c.graminearum at 20ppm when compared to untreated controls showing extensive disease development under the same conditions 1.5.

Claims

1. A compound having formula (I)

Wherein:

g is selected from the group consisting of G-1, G-2, G-3, and G-4, wherein:

R ⁷、R⁸, and R ⁹ are independently selected from hydrogen, fluoro, chloro, bromo, iodo, C _1-4 alkyl, allyl, propargyl, cyclopropylmethyl, cyclopentyl, cyclohexyl, -C (=o) OCH ₃、-C(＝O)N(CH₃)₂, 2- (dimethylamino) -2-oxo-ethyl, 2- (methylamino) -2-oxo-ethyl, difluoromethyl, trifluoromethyl, methylsulfonyl, methylsulfanyl, methoxy, ethoxy, cyano, hydroxy, mercapto, and amino;

Or an agrochemically acceptable salt, stereoisomer, enantiomer, and N-oxide of the compound of formula (I).

2. The compound of claim 1, wherein Q ^a、Q^b、Q^c、Q⁷、Q⁸ and Q ⁹ are as follows:

a) Q ^a is C, Q ^b is N, Q ^c is CH and a single one of Q ⁷、Q⁸ and Q ⁹ is N, or

B) Q ^a is C, Q ^b is N, Q ^c is CH, Q ⁷ is N or CR ⁷,Q⁸ is CR ⁸, and Q ⁹ is N, or

C) Q ^a is N, Q ^b is C, Q ^c is CH, Q ⁷ is CR ⁷, and a single one of Q ⁸ and Q ⁹ is N, or

D) Q ^a is C, Q ^b is N, Q ^c is CH, Q ⁷ is CR ⁷,Q⁸ is CR ⁸, and Q ⁹ is N, or

E) Q ^a is C, Q ^b is N, Q ^c is CH, Q ⁷ is N, Q ⁸ is CR ⁸, and Q ⁹ is N, or

F) Q ^a is N, Q ^b is C, Q ^c is CH, Q ⁷ is CR ⁷,Q⁸ is CR ⁸, and Q ⁹ is N.

3. The compound of claim 1 or claim 2, wherein:

a) Q ^a is C, Q ^b is N, Q ^c is CH, Q ⁷ is CR ⁷,Q⁸ is CR ⁸, and Q ⁹ is N, or

B) Q ^a is C, Q ^b is N, Q ^c is CH, Q ⁷ is N, Q ⁸ is CR ⁸, and Q ⁹ is N, or

C) Q ^a is N, Q ^b is C, Q ^c is CH, Q ⁷ is CR ⁷,Q⁸ is CR ⁸, and Q ⁹ is N.

4. A compound according to any one of claims 1 to 3, wherein R ¹ is phenyl, or phenyl substituted with a single substituent selected from methyl, trifluoromethyl, ethynyl, chloro and cyclopropyl, or 3-cyclopropyl-2-fluorophenyl, or pyridinyl substituted with a single substituent selected from cyano and cyclopropyl.

5. The compound according to any one of claims 1 to 4, wherein G is 2, 4-dimethylphenyl, 2, 4-dichlorophenyl, 4-bromo-2-methylphenyl, 4-bromo-2-chlorophenyl, 2, 6-dichloro-3-pyridinyl, 4, 6-dichloro-3-pyridinyl, 3, 5-dichloro-2-pyridinyl, 3, 5-dichloro-thienyl, 3, 5-dimethyl-thienyl, 3, 4-dimethylphenyl, 2-chloro-4-methylphenyl, 2-bromo-4-chlorophenyl, 4-chloro-2-fluorophenyl, or 2-chloro-4-fluorophenyl.

6. The compound of any one of claims 1 to 5, wherein, independently of each other, R ⁷ is hydrogen, chloro, or methyl, R ⁸ is hydrogen, chloro, fluoro, or methyl, R ⁹ is hydrogen or methyl, provided that when only one of Q ⁷、Q⁸ and Q ⁹ is N, at least one of R ⁷、R⁸ and R ⁹ is hydrogen.

7. The compound of any one of claims 1 to 5, wherein only one of Q ⁷、Q⁸ and Q ⁹ is N, and when present, R ⁷ is hydrogen, chlorine, or methyl, R ⁸ is hydrogen, chlorine, or fluorine, R ⁹ is hydrogen or methyl, provided that at least one of R ⁷、R⁸ and R ⁹ is hydrogen.

8. The compound of any one of claims 1 to 5, wherein two of Q ⁷、Q⁸ and Q ⁹ are nitrogen, R ⁷ and R ⁹ are hydrogen or methyl, and R ⁸ is hydrogen or fluorine.

9. An agrochemical composition comprising a fungicidally effective amount of a compound according to any one of claims 1 to 8.

10. The composition of claim 9, further comprising at least one additional active ingredient and/or an agrochemically acceptable diluent or carrier.

11. A method for controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a fungicidally effective amount of a compound according to any one of claims 1 to 8, or a composition comprising this compound as active ingredient, is applied to the plants, parts thereof or to the locus thereof.

12. Use of a compound according to any one of claims 1 to 8 as a fungicide.

13. Plant propagation material, such as a seed, comprising a compound according to any one of claims 1 to 8 or a composition comprising this compound as active ingredient, or being treated with said compound or said composition, or having said compound or said composition adhered thereto.

14. A compound having the formula (IC-1), (IC-2), or (IC-3):

Wherein X ^a is X ³ or X ⁴;

X ^b and X ^c are both hydrogen, or X ^b is hydrogen and X ^c is a protecting group, or X ^b and X ^c are the same or different protecting groups, or X ^b and X ^c together with the nitrogen to which they are attached form a protecting group, wherein the one or more protecting groups are selected from t-butyloxycarbonyl, benzylcarbonyl, 9-fluorenylmethylcarbonyl, trifluoroacetyl, benzyl, triphenylmethyl, benzylidene and p-toluenesulfonyl, phthalimide, and succinimide;

X ^d is H or-CH ₂-C(O)-CH₂ -G;

x ⁴ is OH or-O-R ¹, and

Wherein R ¹、Q^a、Q^b、Q^c、Q⁷、Q⁸、Q⁹, and G are as defined for a compound of formula (I) according to any one of claims 1 to 8.