CN104177301B - A kind of preparation method of dexrazoxane - Google Patents

Abstract

This invention relates to a method for preparing dexylpropane imine. Addressing the various problems associated with current dexylpropane synthesis routes, such as complexity, high cost, high reaction temperature, low yield, cumbersome post-processing, and long production cycles, this invention provides a simple and efficient method for preparing dexylpropane imine. Starting from (S)-1,2-diaminopropane hydrochloride or (S)-1,2-diaminopropane, only two steps are needed to obtain crude dexylpropane imine with a maximum purity of 99.46%. Simple recrystallization then yields a pure product with a purity of up to 99.96%. This invention is simple to operate and uses suitable temperatures, significantly shortening the synthesis cycle and greatly improving the yield and purity of the product.

Description

A kind of preparation method of dextropropanimine

technical field

The invention belongs to the technical field of drug synthesis, specifically relates to the field of synthesis of antineoplastic drugs, and more specifically relates to a simple and efficient preparation method of dextropropimine.

Background technique

Dexrazoxane chemical name is (S)-(+)-4,4'-(1-methyl-1,2-ethylenediyl)-bis-2,6-piperazinedione, structure As shown in Formula-I:

Dextropropylimine is the d-isomer of propyleneimine (razoxane), also known as dexrazoxane or derazoxan, and is a lipophilic derivative of the chelating agent ethylenediaminetetraacetic acid, which is used clinically for chemical protection It is mainly used to prevent anthracycline-induced cardiotoxicity. The mechanism of cardiotoxicity caused by anthracyclines is mainly due to the generation of reactive oxygen species during the formation of stable complexes between anthracyclines and iron, which cause lipid peroxidation to the myocardium and damage the myocardium. As a cardioprotective agent of chemotherapeutic drugs, dextropropylimine reduces the generation of oxygen free radicals that have toxic effects on myocardial tissue by capturing free iron and iron in iron-anthracycline complexes, thereby reducing the cardiotoxicity of anthracyclines . Dexrazoxane was developed by Chiron Corporation of the United States, first listed in Italy in 1992, and approved by the FDA in 1995 for listing in the United States. At present, dextropropyl imine is the only protective agent clinically used to reduce cardiotoxicity induced by anthracycline antineoplastic drugs.

Witiak et al. reported in J. Med. Chem. 1977:630, the hydrochloride salt of methyl tetraacetate with excess ammonia and sodium methoxide in methanol. Although this method has certain advantages, this method not only has low yield, but also has harsh conditions and is not easy for industrialization.

CN101563329A discloses a method for preparing dextropropimine through cyclization of alkyl tetraacetate in the presence of ammonia and formamide. This method needs to use ammonia gas in production, which has relatively high requirements for personnel protection and tail gas treatment in the production process, and is not easy to be industrialized.

Contents of the invention

The object of the present invention is to provide a kind of simple, efficient preparation method of dextropropanimine. The present invention aims at the problems existing in the current synthesis route of dextropropyl imine such as complex route, high cost, harsh reaction conditions, low yield and low product purity, and proposes a method with simple operation, short route, mild reaction, easy control of conditions, and low cost. A synthesis process of dextropropylimine with low yield, high and stable yield, high purity of crude product and pure product. The crude product dextropropyl imine prepared by the method of the present invention is pure white powder, the purity of the crude product can reach up to 99.46%, and the purity of the refined product can even reach 99.96%. It can be said that the present invention not only greatly reduces the production cost, but also greatly improves the yield and the purity of the product.

The invention provides a kind of method for preparing dextropropyl imine, and its steps are:

(a) reacting the compound of formula-II with formamide in an alkaline solvent, and filtering to obtain the first solid;

(b) the first solid is acidified in an ether solvent, and filtered to obtain a second solid containing dextropropylimine;

R is selected from methyl, ethyl, n-propyl, isopropyl or cyclopropyl; preferably methyl.

As a preference for the above-mentioned method for preparing dextropropylimine, the present invention further discloses the following preferred conditions in step (a), of course, one or more preferred conditions can also be selected individually and non-exclusively according to needs. details as follows:

Preferably, the solvent in the alkaline solvent is selected from one or more of methanol, ethanol, isopropanol, acetone, tetrahydrofuran, and dioxane; more preferably tetrahydrofuran and/or dioxane; most preferably is dioxane;

Preferably, the alkali in the alkaline solvent is selected from one or more of sodium hydride, potassium hydride, sodium methylate, potassium methylate, sodium ethylate, potassium ethylate, sodium tert-butoxide, potassium tert-butoxide; more preferably One or more of sodium hydride, potassium hydride, sodium methoxide or potassium methoxide; most preferably sodium hydride;

Preferably the reaction temperature is 25-80°C;

Preferably the reaction time is 24 to 72 hours;

Preferably, the molar ratio between the compound of formula-II and formamide is 1: (2-10);

Preferably, the molar ratio between the compound of formula-II and the base is 1: (2-12);

Preferably, the concentration of the compound of formula-II in the reaction system is 0.1-0.5 mol/L.

As a preference for the above-mentioned method for preparing dextropropylimine, the present invention further discloses the following preferred conditions in step (b), of course, one or more preferred conditions can also be selected individually and non-exclusively according to needs, which details as follows:

Preferably, the ether solvent is selected from one or more of R ¹ -OR ² ; R ¹ and R ² are independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, iso Butyl or tert-butyl; More preferably ether solvent is selected from one or more in isopropyl ether, methyl tert-butyl ether, ether;

Preferably, the acid used in the acidification is an inorganic acid and/or an organic acid; the acid used in the acidification is selected from one or more of formic acid, acetic acid, benzoic acid, oxalic acid, and succinic acid;

Preferably the acidification is to adjust the pH to 5-8, more preferably 6-8, most preferably 7.

As a preferred method for preparing dextropropylimine, the present invention further discloses the step of obtaining the crude product of dextropropylimine by purifying the second solid containing dextropropylimine:

(c) adding the second solid to the organic solvent, heating, stirring, and filtering to obtain the third filtrate;

(d) After the third filtrate is concentrated, an alcoholic solvent is added to precipitate a solid, which is filtered and dried to obtain crude dextropropimine.

As a preferred method of obtaining the crude product of dextropropylimine from the second solid purification containing dextropropylimine, the present invention further discloses the following preferred conditions, and of course one or more of them can be selected individually and non-exclusively as required A preferred condition is as follows:

Preferably, the organic solvent in step (c) is selected from one or more of methanol, ethanol, isopropanol, acetone, tetrahydrofuran, and dioxane; more preferably tetrahydrofuran and/or dioxane; Dioxane is most preferred; further preferably, the amount of the organic solvent is 1 to 10 times the volume of the solvent in the alkaline solvent in step (a); more preferably 1.5 to 8 times;

Preferably, the heating temperature in step (c) is 40-50°C;

Preferably, the stirring time in step (c) is 10 to 90 minutes; more preferably 20 to 50 minutes, most preferably 30 minutes;

Preferably, the alcoholic solvent described in step (d) is selected from one or more of methanol, ethanol, n-propanol, and isopropanol;

Preferably, the mass percentage of dextropropylimine in the crude product of dextropropylimine obtained in step (d) is not less than 95%.

As a preferred method for the above-mentioned preparation of dextropropylimine, the present invention further discloses a method for purifying the crude product of dextropropylimine to obtain dextropropylimine with a mass percentage not lower than 99%: adding the crude product of dextropropylimine to di Heat to reflux in the six rings, cool to room temperature, filter and separate the precipitated solid, and dry the solid to obtain dextropropimine with a mass percentage of not less than 99%.

The present invention also provides a preparation method of a compound of formula-II: the compound of formula-II is made of (S)-1,2-diaminopropane or its hydrochloride and the compound of formula-III in the presence of potassium carbonate and/or phosphoric acid After reacting in the acetonitrile of potassium, obtain through aftertreatment step;

Preferably, the molar ratio between (S)-1,2-diaminopropane or its hydrochloride and the compound of formula-III is 1: (5-15);

Preferably, the molar ratio between (S)-1,2-diaminopropane or its hydrochloride and potassium carbonate and/or potassium phosphate is 1: (8-12);

Preferably the reaction temperature is 25-50°C, more preferably 50°C;

The preferred reaction time is 4 to 168 hours;

When preparing the compound of formula-II, the raw material (S)-1,2-diaminopropane hydrochloride or (S)-1,2-diaminopropane is equivalent in technical effect, and in the application process, more Preference is given to using (S)-1,2-diaminopropane hydrochloride.

Preferably, the post-treatment steps for isolating the compound of formula-II from the reaction system are: filtering the reactant, concentrating the filtrate, acidifying with an acidifying reagent A, washing with petroleum ether, alkalizing with an alkalizing reagent B, and extracting with an organic solvent C , dried, filtered, and the filtrate was concentrated to obtain the compound of formula-II;

Preferably said acidifying reagent A is 12% HCl solution;

Preferably, the boiling range of the petroleum ether is 60-90°C;

The preferred alkalizing reagent B is selected from one or more of potassium carbonate, sodium carbonate, and 15% NaOH solution;

Preferably, the organic solvent C is selected from one or more of ethyl acetate, dichloromethane, and ether.

As a preferred version of the present invention, the present invention also provides a preferred method for preparing dextropropylimine when R is a methyl group, specifically comprising the following steps:

(a) React (S)-1,2-diaminopropane hydrochloride or (S)-1,2-diaminopropane with methyl bromoacetate in an alkaline solvent at 25-50°C for 4 ~168 hours, filter, concentrate the filtrate, acidify with acidifying reagent A, wash with petroleum ether, alkalinize with alkalizing reagent B, extract with organic solvent C, dry, filter, and concentrate the filtrate to obtain (S)-1,2 - diaminopropane - methyl tetraacetate.

(b) React (S)-1,2-diaminopropane-tetraacetic acid methyl ester with formamide at a suitable reaction concentration in an alkaline solvent at 25-80°C for 24-72 hours, and filter Add the cake to an ether solvent for acidification, then filter, add the filter cake to the organic solvent D, stir for 10-90 minutes under heating conditions, and then filter, add a small amount of alcohol solvent after concentrating the filtrate, solids are precipitated, filter, and collect The filter cake was dried to obtain the crude product dextropropyl imine. The resulting crude product was added to dioxane and heated to reflux, cooled to room temperature and then crystallized, filtered and dried to obtain pure dextropropimine.

Concrete synthetic route is as follows:

Preferably, said step (a) has one or more of the following preferred conditions individually and not exclusively:

The alkali in the alkaline solvent is selected from one or both of potassium carbonate and potassium phosphate, preferably potassium carbonate;

The solvent in the basic solvent is acetonitrile;

The acidifying reagent A is 12% HCl solution;

The boiling range of the petroleum ether is 60-90°C;

The basifying reagent B is selected from one or more of potassium carbonate, sodium carbonate, and 15% NaOH solution;

The organic solvent C is selected from one or more of ethyl acetate, methylene chloride, ether;

The molar ratio between (S)-1,2-diaminopropane hydrochloride or (S)-1,2-diaminopropane and methyl bromoacetate is 1: (5-15);

The molar ratio between (S)-1,2-diaminopropane hydrochloride or (S)-1,2-diaminopropane and alkali is 1: (8-12);

The reaction temperature is preferably 50°C.

The starting material (S)-1,2-diaminopropane hydrochloride or (S)-1,2-diaminopropane used in step (a) is equivalent in technical effect, and in the application process Among them, (S)-1,2-diaminopropane hydrochloride is more preferably used.

The step (b) has one or more of the following preferred conditions independently and not exclusively:

The alkali in the alkaline solvent is selected from one or more of sodium hydride, potassium hydride, sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, sodium tert-butoxide, potassium tert-butoxide; preferably selected from hydrogenation One or more of sodium, potassium hydride, sodium methylate or potassium methylate; most preferably sodium hydride;

The solvent in the alkaline solvent is selected from one or more of methanol, ethanol, isopropanol, acetone, tetrahydrofuran, dioxane; preferably tetrahydrofuran and/or dioxane; most preferably dioxane;

The ether solvent is selected from one or more of R ¹ -OR ² ; R ¹ and R ² are independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl Or tert-butyl; The ether solvent is selected from one or more of isopropyl ether, methyl tert-butyl ether, ether;

Preferably the acid used in the acidification is an inorganic acid and/or an organic acid; the acid used in the acidification is selected from one or more of formic acid, acetic acid, benzoic acid, oxalic acid, succinic acid; preferably the The acidification is to adjust the pH to 5-8, more preferably 6-8, most preferably 7;

The organic solvent D is selected from one or more of methanol, ethanol, isopropanol, acetone, tetrahydrofuran, and dioxane; more preferably tetrahydrofuran and/or dioxane; most preferably dioxane Hexacyclic; more preferably, the amount of the organic solvent D is 1 to 10 times the volume of the solvent in the alkaline solvent in step (a); more preferably 1.5 to 8 times;

Described heating temperature is 40～50 ℃;

The stirring time is 10-90 min, preferably 20-50 min, more preferably 30 min;

The alcoholic solvent is selected from one or more of methanol, ethanol, n-propanol, isopropanol;

The molar ratio between (S)-1,2-diaminopropane-tetraacetic acid methyl ester and formamide is 1: (2-10);

The molar ratio between the (S)-1,2-diaminopropane-tetraacetic acid methyl ester and the base is 1: (2-12);

The reaction concentration of the (S)-1,2-diaminopropane-tetraacetic acid methyl ester is 0.1-0.5 mol/L.

Compared with the existing technology, starting from (S)-1,2-diaminopropane hydrochloride or (S)-1,2-diaminopropane through the technical solution disclosed in the present invention, only two steps are required to The high-purity dextropropylimine can be obtained, which not only shortens the production cycle, but also reduces the production cost. At the same time, through the technical solution disclosed in the present invention, unfavorable reaction conditions such as high temperature, long period, and high toxicity are avoided, and difficult difficulties such as low yield and low purity are difficult to overcome, so that the environmental friendliness of the synthesis process is enhanced. , the utilization rate of raw materials is improved, and the waste of resources is reduced, which is more suitable for the development requirements of modern medicine and more suitable for the harmonious and sustainable development of modern society.

In summary, the adoption of the technical solution disclosed in the present invention makes the synthetic process with the advantages of low temperature, high yield, high purity, low toxicity, low cost, short cycle, easy operation, easy industrialization, etc., have a higher Application value and development prospect.

detailed description

The present invention will be further described below in conjunction with specific embodiments. It should be understood that the following examples are only used to further illustrate the present invention, rather than limit the scope of the present invention.

Embodiment 1: the preparation of (S)-1,2-diaminopropane-tetraacetic acid methyl ester:

Embodiment 1.1

(S)-1,2-diaminopropane hydrochloride (500mg, 3.4mmol, 1eq), methyl bromoacetate (5202mg, 34mmol, 10eq), potassium carbonate (4692mg, 34mmol, 10eq), acetonitrile (34mL, 0.1M) were added to 100mL single-necked bottles, and reacted at 25°C for 24 hours. After the reaction was completed, the inorganic salts were filtered off, the filtrate was concentrated to dryness, and HCl (15mL, 12%) solution was added to acidify, and petroleum ether (15ml×2, 60～90℃), adjusted the pH to 10 with saturated sodium carbonate solution, extracted with dichloromethane (15ml×3), dried and concentrated to dryness to obtain the crude product (S)-1,2-diaminopropane-tetra Methyl acetate, crude product yield 55%.

Embodiment 1.2

(S)-1,2-diaminopropane hydrochloride (500mg, 3.4mmol, 1eq), methyl bromoacetate (5202mg, 34mmol, 10eq), potassium carbonate (4692mg, 34mmol, 10eq), acetonitrile (34mL, 0.1M) were added to 100mL single-necked bottles, and reacted at 25°C for 48 hours. After the reaction was completed, the inorganic salts were filtered off, the filtrate was concentrated to dryness, acidified by adding HCl (15mL, 12%) solution, and petroleum ether (15ml×2, 60～90℃), adjusted the pH to 10 with saturated sodium carbonate solution, extracted with dichloromethane (15ml×3), dried and concentrated to dryness to obtain the crude product (S)-1,2-diaminopropane-tetra Methyl acetate, crude product yield 68%.

Embodiment 1.3

(S)-1,2-diaminopropane hydrochloride (500mg, 3.4mmol, 1eq), methyl bromoacetate (5202mg, 34mmol, 10eq), potassium carbonate (4692mg, 34mmol, 10eq), acetonitrile (34mL, 0.1M) were added to 100mL single-necked bottles, and reacted at 25°C for 72 hours. After the reaction was completed, the inorganic salts were filtered off, the filtrate was concentrated to dryness, acidified by adding HCl (15mL, 12%) solution, and petroleum ether (15ml×2, 60～90℃), adjusted the pH to 10 with saturated sodium carbonate solution, extracted with dichloromethane (15ml×3), dried and concentrated to dryness to obtain the crude product (S)-1,2-diaminopropane-tetra Methyl acetate, crude product yield 81%.

Embodiment 1.4

(S)-1,2-diaminopropane hydrochloride (500mg, 3.4mmol, 1eq), methyl bromoacetate (5202mg, 34mmol, 10eq), potassium carbonate (4692mg, 34mmol, 10eq), acetonitrile (34mL, 0.1M) were added to 100mL single-necked bottles, and reacted at 25°C for 168 hours. After the reaction was completed, the inorganic salts were filtered off, the filtrate was concentrated to dryness, acidified by adding HCl (15mL, 12%) solution, and petroleum ether (15ml×2, 60～90℃), adjusted the pH to 10 with saturated sodium carbonate solution, extracted with dichloromethane (15ml×3), dried and concentrated to dryness to obtain the crude product (S)-1,2-diaminopropane-tetra Methyl acetate, crude product yield 81%.

Embodiment 1.5

(S)-1,2-diaminopropane hydrochloride (500mg, 3.4mmol, 1eq), methyl bromoacetate (2601mg, 17mmol, 5eq), potassium carbonate (4692mg, 34mmol, 10eq), acetonitrile (34mL, 0.1M) were added to 100mL single-necked bottles, and reacted at 25°C for 24 hours. After the reaction was completed, the inorganic salts were filtered off, the filtrate was concentrated to dryness, and HCl (15mL, 12%) solution was added to acidify, and petroleum ether (15ml×2, 60～90℃), adjusted the pH to 10 with saturated sodium carbonate solution, extracted with dichloromethane (15ml×3), dried and concentrated to dryness to obtain the crude product (S)-1,2-diaminopropane-tetra Methyl acetate, crude product yield 32%.

Embodiment 1.6

(S)-1,2-diaminopropane hydrochloride (500mg, 3.4mmol, 1eq), methyl bromoacetate (7803mg, 51mmol, 15eq), potassium carbonate (4692mg, 34mmol, 10eq), acetonitrile (34mL, 0.1M) were added to 100mL single-necked bottles, and reacted at 25°C for 24 hours. After the reaction was completed, the inorganic salts were filtered off, the filtrate was concentrated to dryness, and HCl (15mL, 12%) solution was added to acidify, and petroleum ether (15ml×2, 60～90℃), adjusted the pH to 10 with saturated sodium carbonate solution, extracted with dichloromethane (15ml×3), dried and concentrated to dryness to obtain the crude product (S)-1,2-diaminopropane-tetra Methyl acetate, crude product yield 57%.

Embodiment 1.7

(S)-1,2-diaminopropane (250mg, 3.4mmol, 1eq), methyl bromoacetate (5202mg, 34mmol, 10eq), potassium carbonate (4692mg, 34mmol, 10eq), acetonitrile (34mL, 0.1M) Add them into 100mL single-necked bottles respectively, and react at 25°C for 24 hours. After the reaction is over, filter off the inorganic salts, concentrate the filtrate to dryness, add HCl (15mL, 12%) solution to acidify, and use petroleum ether (15ml×2, 60-90 ℃), washed with saturated sodium carbonate solution to adjust the pH to 10, then extracted with dichloromethane (15ml×3), dried and concentrated to dryness to obtain the crude product (S)-1,2-diaminopropane-tetraacetic acid methyl ester , The crude product yield is 55%.

Embodiment 1.8

(S)-1,2-diaminopropane hydrochloride (500mg, 3.4mmol, 1eq), methyl bromoacetate (5202mg, 34mmol, 10eq), potassium phosphate (5202mg, 34mmol, 10eq), acetonitrile (34mL, 0.1M) were added to 100mL single-necked bottles, and reacted at 25°C for 24 hours. After the reaction was completed, the inorganic salts were filtered off, the filtrate was concentrated to dryness, and HCl (15mL, 12%) solution was added to acidify, and petroleum ether (15ml×2, 60～90℃), adjusted the pH to 10 with saturated sodium carbonate solution, extracted with dichloromethane (15ml×3), dried and concentrated to dryness to obtain the crude product (S)-1,2-diaminopropane-tetra Methyl acetate, crude product yield 47%.

Embodiment 1.9

(S)-1,2-diaminopropane hydrochloride (500mg, 3.4mmol, 1eq), methyl bromoacetate (5202mg, 34mmol, 10eq), potassium phosphate (5202mg, 34mmol, 10eq), acetonitrile (34mL, 0.1M) were added to 100mL single-necked bottles, and reacted at 25°C for 168 hours. After the reaction was completed, the inorganic salts were filtered off, the filtrate was concentrated to dryness, acidified by adding HCl (15mL, 12%) solution, and petroleum ether (15ml×2, 60～90℃), adjusted the pH to 10 with saturated sodium carbonate solution, extracted with dichloromethane (15ml×3), dried and concentrated to dryness to obtain the crude product (S)-1,2-diaminopropane-tetra Methyl acetate, crude product yield 73%.

Embodiment 1.10

(S)-1,2-diaminopropane hydrochloride (500mg, 3.4mmol, 1eq), methyl bromoacetate (2601mg, 17mmol, 5eq), potassium carbonate (4692mg, 34mmol, 10eq), acetonitrile (34mL, 0.1M) were added to 100mL single-necked bottles, and reacted at 50°C for 6 hours. After the reaction was completed, the inorganic salts were filtered off, the filtrate was concentrated to dryness, and HCl (15mL, 12%) solution was added to acidify, and petroleum ether (15ml×2, 60～90℃), adjusted the pH to 10 with saturated sodium carbonate solution, extracted with dichloromethane (15ml×3), dried and concentrated to dryness to obtain the crude product (S)-1,2-diaminopropane-tetra Methyl acetate, crude product yield 81%.

Embodiment 1.11

(S)-1,2-diaminopropane hydrochloride (500mg, 3.4mmol, 1eq), methyl bromoacetate (2601mg, 17mmol, 5eq), potassium carbonate (4692mg, 34mmol, 10eq), acetonitrile (34mL, 0.1M) were added to 100mL single-necked bottles, and reacted at 50°C for 4 hours. After the reaction was completed, the inorganic salts were filtered off, the filtrate was concentrated to dryness, and HCl (15mL, 12%) solution was added to acidify, and petroleum ether (15ml×2, 60～90℃), adjusted the pH to 10 with saturated sodium carbonate solution, extracted with dichloromethane (15ml×3), dried and concentrated to dryness to obtain the crude product (S)-1,2-diaminopropane-tetra Methyl acetate, crude product yield 81%.

Embodiment 1.12

(S)-1,2-diaminopropane hydrochloride (500mg, 3.4mmol, 1eq), methyl bromoacetate (2601mg, 17mmol, 5eq), potassium carbonate (4692mg, 34mmol, 10eq), acetonitrile (11mL, 0.3M) were added to 100mL single-necked bottles, and reacted at 50°C for 2 hours. After the reaction was completed, the inorganic salts were filtered off, the filtrate was concentrated to dryness, acidified by adding HCl (15mL, 12%) solution, and petroleum ether (15ml×2, 60～90℃), adjusted the pH to 10 with saturated sodium carbonate solution, extracted with dichloromethane (15ml×3), dried and concentrated to dryness to obtain the crude product (S)-1,2-diaminopropane-tetra Methyl acetate, crude product yield 70%.

Embodiment 1.13

(S)-1,2-diaminopropane hydrochloride (500mg, 3.4mmol, 1eq), methyl bromoacetate (2601mg, 17mmol, 5eq), potassium carbonate (4692mg, 34mmol, 10eq), acetonitrile (34mL, 0.1M) were added to 100mL single-necked bottles, and reacted at 80°C for 4 hours. After the reaction was completed, the inorganic salts were filtered off, the filtrate was concentrated to dryness, and HCl (15mL, 12%) solution was added to acidify, and petroleum ether (15ml×2, 60～90℃), adjusted the pH to 10 with saturated sodium carbonate solution, extracted with dichloromethane (15ml×3), dried and concentrated to dryness to obtain the crude product (S)-1,2-diaminopropane-tetra Methyl acetate, crude product yield 74%.

Embodiment 1.14

(S)-1,2-diaminopropane hydrochloride (500mg, 3.4mmol, 1eq), methyl bromoacetate (2601mg, 17mmol, 5eq), potassium carbonate (3754mg, 27.2mmol, 8eq), acetonitrile (11mL , 0.3M) were added to 100mL single-necked bottles, and reacted at 50°C for 4 hours. After the reaction was completed, the inorganic salts were filtered off, the filtrate was concentrated to dryness, acidified by adding HCl (15mL, 12%) solution, and petroleum ether (15ml×2 , 60-90°C), washed with saturated sodium carbonate solution to adjust the pH to 10, then extracted with dichloromethane (15ml×3), dried and concentrated to dryness to obtain the crude product (S)-1,2-diaminopropane- Methyl tetraacetate, crude product yield 74%.

Embodiment 1.15

(S)-1,2-diaminopropane hydrochloride (500mg, 3.4mmol, 1eq), methyl bromoacetate (2601mg, 17mmol, 5eq), potassium carbonate (3754mg, 27.2mmol, 8eq), acetonitrile (11mL , 0.3M) were added to 100mL single-necked bottles, and reacted at 50°C for 5 hours. After the reaction was completed, the inorganic salts were filtered off, the filtrate was concentrated to dryness, acidified by adding HCl (15mL, 12%) solution, and petroleum ether (15ml×2 , 60-90°C), washed with saturated sodium carbonate solution to adjust the pH to 10, then extracted with dichloromethane (15ml×3), dried and concentrated to dryness to obtain the crude product (S)-1,2-diaminopropane- Methyl tetraacetate, crude product yield 68%.

Embodiment 1.16

(S)-1,2-diaminopropane hydrochloride (500mg, 3.4mmol, 1eq), methyl bromoacetate (2601mg, 17mmol, 5eq), potassium carbonate (5630mg, 40.8mmol, 12eq), acetonitrile (11mL , 0.3M) were added to 100mL single-necked bottles, and reacted at 50°C for 4 hours. After the reaction was completed, the inorganic salts were filtered off, the filtrate was concentrated to dryness, acidified by adding HCl (15mL, 12%) solution, and petroleum ether (15ml×2 , 60-90°C), washed with saturated sodium carbonate solution to adjust the pH to 10, then extracted with dichloromethane (15ml×3), dried and concentrated to dryness to obtain the crude product (S)-1,2-diaminopropane- Methyl tetraacetate, crude product yield 73%.

Embodiment 1.17

(S)-1,2-diaminopropane hydrochloride (500mg, 3.4mmol, 1eq), methyl bromoacetate (4162mg, 27.2mmol, 8eq), potassium carbonate (4692mg, 34mmol, 10eq), acetonitrile (34mL , 0.1M) were added to 100mL single-necked bottles, and reacted at 50°C for 4 hours. After the reaction was completed, the inorganic salts were filtered off, the filtrate was concentrated to dryness, acidified by adding HCl (15mL, 12%) solution, and petroleum ether (15ml×2 , 60-90°C), washed with saturated sodium carbonate solution to adjust the pH to 10, then extracted with dichloromethane (15ml×3), dried and concentrated to dryness to obtain the crude product (S)-1,2-diaminopropane- Methyl tetraacetate, crude product yield 81%.

Embodiment 1.18

(S)-1,2-diaminopropane hydrochloride (500mg, 3.4mmol, 1eq), methyl bromoacetate (5202mg, 34mmol, 10eq), potassium carbonate (4692mg, 34mmol, 10eq), acetonitrile (34mL, 0.1M) were added to 100mL single-necked bottles, and reacted at 50°C for 4 hours. After the reaction was completed, the inorganic salts were filtered off, the filtrate was concentrated to dryness, and HCl (15mL, 12%) solution was added to acidify, and petroleum ether (15ml×2, 60～90℃), adjusted the pH to 10 with saturated sodium carbonate solution, extracted with dichloromethane (15ml×3), dried and concentrated to dryness to obtain the crude product (S)-1,2-diaminopropane-tetra Methyl acetate, crude product yield 81%.

Embodiment 1.19

(S)-1,2-diaminopropane hydrochloride (500mg, 3.4mmol, 1eq), methyl bromoacetate (5202mg, 34mmol, 10eq), potassium carbonate (4692mg, 34mmol, 10eq), acetonitrile (34mL, 0.1M) were added to 100mL single-necked bottles, and reacted at 50°C for 6 hours. After the reaction was completed, the inorganic salts were filtered off, the filtrate was concentrated to dryness, and HCl (15mL, 12%) solution was added to acidify, and petroleum ether (15ml×2, 60～90℃), adjusted the pH to 10 with saturated sodium carbonate solution, extracted with dichloromethane (15ml×3), dried and concentrated to dryness to obtain the crude product (S)-1,2-diaminopropane-tetra Methyl acetate, crude product yield 83%.

Embodiment 2: the content detection of (S)-1,2-diaminopropane-methyl tetraacetate:

HPLC condition 1 provided by the present invention is:

Chromatographic column: Kaseisorb LCODS (4.6×150mmФ5μm)

Eluent: CH ₃ CN:H ₂ O=30:70

Detection wavelength: 210nm

Flow rate: 1.0mL/min

Time: 20min

Using HPLC condition 1, the content of (S)-1,2-diaminopropane-methyl tetraacetate obtained in Example 1 is detected, and the experimental results are shown in Table 1:

The content detection result of table 1 (S)-12-diaminopropane-methyl tetraacetate

Example 1 program serial number content(%) Embodiment 1.11 66 Embodiment 1.14 63 Embodiment 1.15 60 Embodiment 1.17 89 Embodiment 1.18 90 Embodiment 1.19 89

Embodiment 3: the preparation of dextropropanimine:

Dissolve (S)-1,2-diaminopropane-tetraacetic acid methyl ester (2000mg, 5.5mmol, 1eq, 0.1M) in dioxane (18ml, sodium treatment) solution at room temperature, slowly added dropwise to dioxane (37ml, treated with sodium) solution dissolved in sodium hydride (2640mg, 66mmol, 12eq, active ingredient 60%*), and reacted at 25°C under nitrogen protection for 24 hour, the reaction is over. Filter, wash with anhydrous ether (20ml×2), add the filter cake to anhydrous ether (55ml), adjust the pH to 7 with formic acid, filter, add the filter cake to dioxane (100ml, untreated ), stirred at 50°C for 30min, filtered, concentrated the filtrate to dryness, added a small amount of methanol (2-3ml) and stood still, the solid was precipitated, filtered, and dried to obtain the crude dextropropimine as a white powder. The yield of the crude product was was 31%.

*Unless otherwise specified, the active ingredient of sodium hydride described in Examples 3-19 is 60%.

Embodiment 4: the preparation of dextropropanimine:

Dissolve (S)-1,2-diaminopropane-tetraacetic acid methyl ester (2000mg, 5.5mmol, 1eq, 0.1M) in dioxane (18ml, sodium Treatment) solution was slowly added dropwise at room temperature to a solution of dioxane (37ml, treated with sodium) dissolved in sodium hydride (1080mg, 27.5mmol, 5eq), and reacted at 25°C under nitrogen protection for 24 hours, and the reaction was completed. Filter, wash with anhydrous ether (20ml×2), add the filter cake to anhydrous ether (55ml), adjust the pH to 7 with formic acid, filter, add the filter cake to dioxane (100ml, untreated ), stirred at 50°C for 30min, filtered, concentrated the filtrate to dryness, added a small amount of methanol (2-3ml) and stood still, the solid was precipitated, filtered, and dried to obtain the crude dextropropimine as a white powder. The yield of the crude product was 30%.

Embodiment 5: the preparation of dextropropanimine:

Dissolve (S)-1,2-diaminopropane-tetraacetic acid methyl ester (2000mg, 5.5mmol, 1eq, 0.3M) in dioxane (5ml, sodium Treatment) solution was slowly added dropwise at room temperature to a solution of dioxane (13ml, treated with sodium) dissolved in sodium hydride (1080mg, 27.5mmol, 5eq), and reacted under nitrogen protection at 25°C for 24 hours, and the reaction was completed. Filter, wash with anhydrous ether (20ml×2), add the filter cake to anhydrous ether (55ml), adjust the pH to 7 with formic acid, filter, add the filter cake to dioxane (100ml, untreated ), stirred at 50°C for 30min, filtered, concentrated the filtrate to dryness, added a small amount of methanol (2-3ml) and stood still, the solid was precipitated, filtered, and dried to obtain the crude dextropropimine as a white powder. The yield of the crude product was 56%.

Embodiment 6: the preparation of dextropropanimine:

Dissolve (S)-1,2-diaminopropane-tetraacetic acid methyl ester (2000mg, 5.5mmol, 1eq, 0.4M) and formamide (990mg, 22mmol, 4eq) in dioxane (3ml, sodium Treatment) solution was slowly added dropwise at room temperature to a solution of dioxane (10ml, treated with sodium) dissolved in sodium hydride (1080mg, 27.5mmol, 5eq), reacted at 25°C for 24 hours under nitrogen protection, and the reaction was completed. Filter, wash with anhydrous ether (20ml×2), add the filter cake to anhydrous ether (55ml), adjust the pH to 7 with formic acid, filter, add the filter cake to dioxane (100ml, untreated ), stirred at 50°C for 30min, filtered, concentrated the filtrate to dryness, added a small amount of methanol (2-3ml) and stood still, the solid was precipitated, filtered, and dried to obtain the crude dextropropimine as a white powder. The yield of the crude product was 56%.

Embodiment 7: the preparation of dextropropanimine:

Dissolve (S)-1,2-diaminopropane-tetraacetic acid methyl ester (2000mg, 5.5mmol, 1eq, 0.3M) in dioxane (5ml, sodium Treatment) solution was slowly added dropwise at room temperature to a solution of dioxane (13ml, treated with sodium) dissolved in sodium hydride (1080mg, 27.5mmol, 5eq), reacted at 25°C under nitrogen protection for 48 hours, and the reaction ended. Filter, wash with anhydrous ether (20ml×2), add the filter cake to anhydrous ether (55ml), adjust the pH to 7 with formic acid, filter, add the filter cake to dioxane (100ml, untreated ), stirred at 50°C for 30min, filtered, concentrated the filtrate to dryness, added a small amount of methanol (2-3ml) and stood still, the solid was precipitated, filtered, and dried to obtain the crude dextropropimine as a white powder. The yield of the crude product was 59%.

Embodiment 8: the preparation of dextropropanimine:

Dissolve (S)-1,2-diaminopropane-tetraacetic acid methyl ester (2000mg, 5.5mmol, 1eq, 0.3M) in dioxane (5ml, sodium Treatment) solution was slowly added dropwise at room temperature to a solution of dioxane (13ml, treated with sodium) dissolved in sodium hydride (1080mg, 27.5mmol, 5eq), reacted at 25°C under nitrogen protection for 72 hours, and the reaction ended. Filter, wash with anhydrous ether (20ml×2), add the filter cake to anhydrous ether (55ml), adjust the pH to 7 with formic acid, filter, add the filter cake to dioxane (100ml, untreated ), stirred at 50°C for 30min, filtered, concentrated the filtrate to dryness, added a small amount of ethanol (2-3ml) and stood still, the solid was precipitated, filtered, and drained to obtain the crude product dextropropylimine as a white powder, the crude product yield 64%.

Embodiment 9: the preparation of dextropropanimine:

Dissolve (S)-1,2-diaminopropane-tetraacetic acid methyl ester (2000mg, 5.5mmol, 1eq, 0.3M) in dioxane (5ml, sodium Treatment) solution was slowly added dropwise at room temperature to a solution of dioxane (13ml, treated with sodium) dissolved in sodium hydride (1320mg, 33mmol, 6eq), and reacted at 25°C for 24 hours under nitrogen protection, and the reaction was completed. Filter, wash with anhydrous ether (20ml×2), add the filter cake to anhydrous ether (55ml), adjust the pH to 7 with acetic acid, filter, add the filter cake to dioxane (100ml, untreated ), stirred at 50°C for 30min, filtered, concentrated the filtrate to dryness, added a small amount of methanol (2-3ml) and stood still, the solid was precipitated, filtered, and dried to obtain the crude dextropropimine as a white powder. The yield of the crude product was 50%.

Embodiment 10: the preparation of dextropropanimine:

Dissolve (S)-1,2-diaminopropane-tetraacetic acid methyl ester (2000mg, 5.5mmol, 1eq, 0.3M) and formamide (742mg, 16.5mmol, 3eq) in dioxane (5ml, via Sodium treatment) solution, slowly added dropwise at room temperature to dioxane (13ml, sodium treatment) solution dissolved with sodium hydride (880mg, 22mmol, 4eq), reacted at 25°C under nitrogen protection for 24 hours, and the reaction was completed. Filter, wash with anhydrous ether (20ml×2), add the filter cake to anhydrous ether (55ml), adjust the pH to 7 with formic acid, filter, add the filter cake to dioxane (100ml, untreated ), stirred at 50°C for 30min, filtered, concentrated the filtrate to dryness, added a small amount of methanol (2-3ml) and stood still, the solid was precipitated, filtered, and dried to obtain the crude dextropropimine as a white powder. The yield of the crude product was 50%.

Embodiment 11: the preparation of dextropropanimine:

Dissolve (S)-1,2-diaminopropane-tetraacetic acid methyl ester (2000mg, 5.5mmol, 1eq, 0.3M) and formamide (1238mg, 27.5mmol, 5eq) in dioxane (5ml, via Sodium treatment) solution, at room temperature, slowly added dropwise to dioxane (13ml, sodium treatment) solution dissolved with sodium hydride (1320mg, 33mmol, 6eq), and reacted under nitrogen protection at 25°C for 24 hours, and the reaction was completed. Filter, wash with anhydrous ether (20ml×2), add the filter cake to anhydrous ether (55ml), adjust the pH to 7 with formic acid, filter, add the filter cake to dioxane (100ml, untreated ), stirred at 50°C for 30 minutes, filtered, concentrated the filtrate to dryness, added a small amount of isopropanol (2-3ml) and stood still, the solid precipitated, filtered, and dried to obtain the crude product dextropropimine, which was a white powder. The yield was 56%.

Embodiment 12: the preparation of dextropropanimine:

Dissolve (S)-1,2-diaminopropane-tetraacetic acid methyl ester (2000mg, 5.5mmol, 1eq, 0.3M) in dioxane (5ml, sodium Treatment) solution was slowly added dropwise at room temperature to a solution of dioxane (13ml, treated with sodium) dissolved in sodium hydride (880mg, 22mmol, 4eq), reacted at 25°C for 24 hours under nitrogen protection, and the reaction ended. Filter, wash with anhydrous ether (20ml×2), add the filter cake to anhydrous ether (55ml), adjust the pH to 7 with benzoic acid, filter, add the filter cake to dioxane (100ml, without treatment), stirring at 50°C for 30 min, filtering, concentrating the filtrate to dryness, adding a small amount of methanol (2-3ml) and standing still, the solid precipitated, filtering, and drying to obtain the crude product dextropropimine as a white powder, the crude product was collected The rate is 56%.

Embodiment 13: the preparation of dextropropanimine:

A solution of (S)-1,2-diaminopropane-tetraacetic acid methyl ester (2000mg, 5.5mmol, 1eq, 0.4M) and formamide (990mg, 22mmol, 4eq) in tetrahydrofuran (3ml, treated with sodium) , was slowly added dropwise to a solution of sodium hydride (1080mg, 27.5mmol, 5eq) in dioxane (10ml, treated with sodium) at room temperature, and reacted at 25°C for 24 hours under nitrogen protection, and the reaction was completed. Filter, wash with anhydrous ether (20ml×2), add the filter cake to anhydrous ether (55ml), adjust the pH to 7 with formic acid, filter, add the filter cake to tetrahydrofuran (100ml, untreated), Stir at 50°C for 90 minutes, filter, concentrate the filtrate to dryness, add a small amount of methanol (2-3ml) and let it stand still, the solid precipitates, filter, and drain to obtain the crude product dextropropylimine as a white powder, the yield of the crude product is 44% .

Embodiment 14: the preparation of dextropropanimine:

Dissolve (S)-1,2-diaminopropane-tetraacetic acid methyl ester (2000mg, 5.5mmol, 1eq, 0.3M) in dioxane (5ml, sodium Treatment) solution was slowly added dropwise at room temperature to a solution of dioxane (13ml, treated with sodium) dissolved in sodium methoxide (1485mg, 27.5mmol, 5eq), and reacted under nitrogen protection at 25°C for 24 hours, and the reaction ended. Filter, wash with anhydrous ether (20ml×2), add the filter cake to anhydrous ether (55ml), adjust the pH to 7 with formic acid, filter, add the filter cake to dioxane (100ml, untreated ), stirred at 50°C for 30min, filtered, concentrated the filtrate to dryness, added a small amount of methanol (2-3ml) and stood still, the solid was precipitated, filtered, and dried to obtain the crude dextropropimine as a white powder. The yield of the crude product was 28%.

Embodiment 15: the preparation of dextropropanimine:

Dissolve (S)-1,2-diaminopropane-tetraacetic acid methyl ester (2000mg, 5.5mmol, 1eq, 0.4M) and formamide (990mg, 22mmol, 4eq) in dioxane (3ml, sodium Treatment) solution was slowly added dropwise at room temperature to a solution of dioxane (10ml, treated with sodium) dissolved in sodium hydride (1080mg, 27.5mmol, 5eq), reacted at 50°C under nitrogen protection for 24 hours, and the reaction ended. Filter, wash with anhydrous ether (20ml×2), add the filter cake to anhydrous ether (55ml), adjust the pH to 7 with formic acid, filter, add the filter cake to dioxane (100ml, untreated ), stirred at 50°C for 30min, filtered, concentrated the filtrate to dryness, added a small amount of methanol (2-3ml) and stood still, the solid was precipitated, filtered, and dried to obtain the crude dextropropimine as a white powder. The yield of the crude product was 60%.

Embodiment 16: the preparation of dextropropanimine:

Dissolve (S)-1,2-diaminopropane-tetraacetic acid methyl ester (2000mg, 5.5mmol, 1eq, 0.3M) in dioxane (5ml, sodium Treatment) solution was slowly added dropwise at room temperature to a solution of dioxane (13ml, treated with sodium) dissolved in sodium hydride (880mg, 22mmol, 4eq), reacted at 80°C for 24 hours under nitrogen protection, and the reaction was completed. Filter, wash with anhydrous ether (20ml×2), add the filter cake to anhydrous ether (55ml), adjust the pH to 7 with formic acid, filter, add the filter cake to dioxane (100ml, untreated ), stirred at 50°C for 30 minutes, filtered, concentrated the filtrate to dryness, added a small amount of methanol (2-3ml) and stood still, precipitated a solid, filtered, and dried to obtain crude dextropropylimine, which was a white powder with a slight yellowish tint. Crude yield was 62%.

Embodiment 17: the preparation of dextropropanimine:

Dissolve (S)-1,2-diaminopropane-tetraacetic acid methyl ester (2000mg, 5.5mmol, 1eq, 0.3M) and formamide (742mg, 16.5mmol, 3eq) in dioxane (5ml, via sodium treatment) solution at room temperature, slowly added dropwise to dioxane (13ml, sodium treatment) solution dissolved with sodium hydride (660mg, 16.5mmol, 3eq), and reacted at 50°C under nitrogen protection for 24 hours, and the reaction ended . Filter, wash with anhydrous ether (20ml×2), add the filter cake to anhydrous ether (55ml), adjust the pH to 7 with formic acid, filter, add the filter cake to dioxane (100ml, untreated ), stirred at 50°C for 30min, filtered, concentrated the filtrate to dryness, added a small amount of methanol (2-3ml) and stood still, the solid was precipitated, filtered, and dried to obtain the crude dextropropimine as a white powder. The yield of the crude product was 66%.

Embodiment 18: the preparation of dextropropanimine:

Dioxane (5ml, Treated with sodium) solution, slowly added dropwise at room temperature to a solution of dioxane (13ml, treated with sodium) dissolved in sodium hydride (552mg, 13.8mmol, 2.5eq), reacted at 50°C for 24 hours under nitrogen protection, The reaction is over. Filter, wash with anhydrous ether (20ml×2), add the filter cake to anhydrous ether (55ml), adjust the pH to 7 with formic acid, filter, add the filter cake to dioxane (100ml, untreated ), stirred at 50°C for 30min, filtered, concentrated the filtrate to dryness, added a small amount of methanol (2-3ml) and stood still, the solid was precipitated, filtered, and dried to obtain the crude dextropropylimine as a white powder. The yield of the crude product was was 44%.

Embodiment 19: the preparation of dextropropanimine:

Dioxane (5ml, without Treatment) solution was slowly added dropwise at room temperature to a solution of dioxane (13ml, untreated) dissolved in sodium hydride (880mg, 22mmol, 4eq), reacted at 25°C under nitrogen protection for 72 hours, and the reaction was completed. Filter, wash with anhydrous ether (20ml×2), add the filter cake to anhydrous ether (55ml), adjust the pH to 7 with formic acid, filter, add the filter cake to dioxane (100ml, untreated ), stirred at 50°C for 30min, filtered, concentrated the filtrate to dryness, added a small amount of methanol (2-3ml) and stood still, the solid was precipitated, filtered, and dried to obtain the crude dextropropimine as a white powder. The yield of the crude product was 62%.

Embodiment 20: the purification of dextropropanimine:

Add the crude dextranimine (2000mg) into dioxane (6-7ml), heat to dissolve, cool to crystallize, filter to obtain a refined white solid, and dry it under reduced pressure at 50°C for 3 hours to obtain 1450-1650mg High-purity dextropropylimine (purity 99.89-99.99%).

Example 21: Detection of the purity of the crude product of dextropropylimine:

HPLC condition 2 provided by the present invention is:

Chromatographic column: EclipseXDB-C18 (4.6×150mmФ5μm)

Eluent: MeOH:0.01mol/LK ₂ PO ₄ =15:85

Detection wavelength: 208nm

Flow rate: 1.0mL/min

Time: 20min

Using HPLC condition 2, the crude product of dextropropyl imine is detected, and the experimental results are shown in Table 2:

The purity detection result of table 2 dextropropimine crude product

Example serial number purity(%) 5 96.91 6 96.27 7 96.98 17 99.46

The above analysis data proves that the yield of the crude product of dextropropylimine obtained according to the method of the present invention can reach up to 66%, and the purity of the crude product is higher than 96%, up to 99.46%, and all higher than 99.89% after purification.

The elemental analysis of the finished product of dextropropylimine is as follows, molecular formula: C ₁₁ H ₁₆ N ₄ O ₄ ; calculated value: carbon 49.25%; hydrogen 6.01%; nitrogen 20.88%; measured value: carbon 48.89%; hydrogen 5.98%; nitrogen 20.70%. The NMR data are as follows: ¹ HNMR(400MHz,d ₆ -DMSO):δ11.05(s,1H),10.98(s,1H),3.43-3.27(m,8H),3.04(dd,J=13.3,6.6Hz ,1H),2.59(dd,J=12.9,7.8Hz,1H),2.33(dd,J=13.0,6.1Hz,1H),0.89(d,J=6.5Hz,3H); ¹³ CNMR(100MHz,d ₆ -DMSO): δ172.40, 171.87, 57.93, 55.59, 53.87, 51.75, 12.98.

The technical means disclosed in the solution of the present invention are not limited to the technical means disclosed above, but also include technical solutions composed of any combination of the above technical features.

The above is the specific implementation of the present invention, it should be pointed out that for those of ordinary skill in the art, without departing from the principle of the present invention, some improvements and modifications can also be made, and these improvements and modifications are also considered It is the scope of protection of this invention.

Claims (8)

1. A method for preparing dextropropanimine, the steps of which are: (1), when neutralizing in a solvent at 25-80°C, react the compound of formula-II, formamide and alkali for 24-72 hours, and filter; The molar ratio of the compound of formula-II, formamide and base is 1:(2～10):(2～12); the base is selected from sodium hydride, potassium hydride, sodium methylate, potassium methylate, sodium ethylate, One of potassium ethylate, sodium tert-butoxide, potassium tert-butoxide or their mixture; the solvent is selected from one of methanol, ethanol, isopropanol, acetone, tetrahydrofuran, dioxane or their Mixed solvent; (2), the product of step (1) is acidified in an ether solvent, and the product is purified; R is selected from methyl, ethyl, n-propyl, isopropyl or cyclopropyl; The ether solvent is selected from one or more of R ¹ -OR ² ; R ¹ and R ² are independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl base or tert-butyl; The acidification is to adjust the pH of the reaction solution to 5-8 with an acid; the acid is an inorganic acid, an organic acid or a mixture thereof; the organic acid is selected from formic acid, acetic acid, benzoic acid, oxalic acid, One of the succinic acids or their mixed acids. 2. The method for preparing dextropropylimine according to claim 1, characterized in that the solvent described in step (1) is selected from tetrahydrofuran, dioxane or their mixed solvents. 3. The method for preparing dextropropylimine according to claim 1, characterized in that the purification described in step (2) is to recrystallize the reaction product in an organic solvent. 4. the method for preparing dextropropyl imine according to claim 3 is characterized in that described recrystallization is reaction product in organic solvent, heating, stirring, filtering, after concentrating, add alcoholic solvent, separate out solid, filter, dry; The organic solvent is selected from one or more of methanol, ethanol, isopropanol, acetone, tetrahydrofuran, and dioxane; The alcohol solvent is selected from one or more of methanol, ethanol, n-propanol and isopropanol. 5. The method for preparing dextropropyl imine according to claim 4, characterized in that the heating temperature in the recrystallization is 40-80° C., and the stirring time is 10-90 min. 6. The method for preparing dextropropyl imine according to claim 4, characterized in that the dried product is added to dioxane and heated to reflux, cooled to room temperature, and the precipitated solid is separated by filtration. 7. the method for preparing dextropropylimine according to claim 1 is characterized in that described formula-II compound is contained in (S)-1,2-diaminopropane or its hydrochloride and formula-III compound Potassium carbonate or potassium phosphate in acetonitrile, reacted for 4-168 hours at 25-50°C, and obtained through post-treatment purification steps; The molar ratio of (S)-1,2-diaminopropane or its hydrochloride to the compound of formula-III is 1: (5-15); The molar ratio of (S)-1,2-diaminopropane or its hydrochloride to potassium carbonate or potassium phosphate is 1:(8-12). 8. The method for preparing dextropropylimine according to claim 7, characterized in that the post-treatment purification step is: the reactant is filtered, concentrated, acidified with acidifying reagent A, washed with sherwood oil, and then alkalized reagent B Alkalizing, extracting with organic solvent C, drying, filtering, and concentrating the filtrate to obtain the compound of formula-II; the acidifying reagent A is 12% HCl solution; the boiling range of the petroleum ether is 60-90°C; the alkali The chemical reagent B is selected from potassium carbonate, sodium carbonate or 15% NaOH solution; the organic solvent C is selected from one of ethyl acetate, dichloromethane, ether or their mixed solvents.