Preparation method of (S)-3-aminobutyronitrile hydrochloride compound

Abstract

The invention discloses a preparation method of (S)-3-aminobutyronitrile hydrochloride compounds, and relates to the technical field of medicine preparation methods. The method comprises the following steps: taking (S)-2-methyl aziridine as an initial raw material, and reacting with sulfonyl chloride in the presence of alkali to obtain an N-sulfonylation intermediate; then, carrying out selective ring opening by adopting diethylaluminium cyanide under a low-temperature condition, and introducing cyano to generate a corresponding cyano-amino intermediate; and removing silicon-based protection by tetra-n-butylammonium fluoride, and salifying by hydrogen chloride to obtain a target product. The method is mild in condition, good in selectivity, high in yield, convenient for large-scale production, high in optical purity of the obtained product and suitable for industrial preparation.

Description

Technical Field

[0001] This invention relates to the field of drug preparation methods, specifically to a method for preparing (S)-3-aminobutyronitrile hydrochloride compounds. Background Technology

[0002] (S)-3-aminobutyronitrile hydrochloride is an important chiral pharmaceutical intermediate containing a chiral primary amine center and a terminal cyano group. It is a key chiral building block in the synthesis of dipeptidyl peptidase-4 (DPP-4) inhibitors of antidiabetic drugs (such as sitagliptin and its derivatives). The optical purity of this compound directly affects the pharmacological activity and safety of the final drug; therefore, developing a preparation method with high optical purity, high yield, and suitability for industrial production has significant economic and social value.

[0003] In existing technologies, the preparation of (S)-3-aminobutyronitrile hydrochloride mainly employs enzymatic resolution or enamine reduction. Enzymatic resolution typically uses racemic compounds as raw materials, utilizing lipases or acylases for kinetic resolution. However, this method suffers from drawbacks such as a low theoretical yield limit (maximum 50%), high cost of enzyme catalysts, harsh reaction conditions, and difficulty in recycling. Chemical reduction methods often use 3-aminobutyronitrile as a starting material, employing asymmetric hydrogenation reduction via chiral catalysts (such as ruthenium and rhodium complexes). However, these methods often involve high-pressure equipment, expensive precious metal catalysts, and the products are often oily substances, making purification difficult. They are also prone to intramolecular cyclization to generate pyrrolidone byproducts or racemization, leading to a decrease in optical purity. Furthermore, existing processes generally require multiple column chromatography steps during purification, resulting in high solvent consumption, which is difficult to meet the requirements of industrial-scale production.

[0004] Therefore, there is an urgent need to develop a new method that is mild in reaction conditions, simple in operation, low in cost, and can obtain high optical purity (S)-3-aminobutyronitrile hydrochloride with high selectivity, in order to overcome the technical defects of existing technologies such as low yield, difficult purification, easy racemization, and unsuitability for industrial production. Summary of the Invention

[0005] The purpose of this invention is to address the problems existing in the prior art by providing a method for preparing (S)-3-aminobutyronitrile hydrochloride compounds. The method involves using (S)-2-methylaziridine and 2-(triphenylsilyl)ethane-1-sulfonyl chloride as starting materials, and proceeding through a three-step reaction involving the addition of a protecting group, selective ring opening, deprotection, and salt formation.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A method for preparing (S)-3-aminobutyronitrile hydrochloride compounds, wherein the method uses (S)-2-methylaziridine and 2-(triphenylsilyl)ethane-1-sulfonyl chloride as starting materials, and prepares (S)-3-aminobutyronitrile hydrochloride through a three-step reaction of adding a protecting group, selective ring opening, deprotection and salt formation. Step 1, the product in the upper protecting group is: (S)-2-(triphenylsilyl)ethane-1-sulfonyl-2-methylaziridine; Step two, the selectively ring-opening product is: (S)-N-(1-cyanopropan-2-yl)-2-(triphenylsilyl)ethane-1-sulfonamide; The structure of (S)-2-(triphenylsilyl)ethane-1-sulfonyl-2-methylaziridine is as follows: ; The structure of the (S)-N-(1-cyanopropan-2-yl)-2-(triphenylsilyl)ethane-1-sulfonamide is as follows: .

[0007] Furthermore, the synthetic route for step one is as follows: ; In step one, N,N-diisopropylethylamine is used as a bound acid. The solvent used in step one is anhydrous dichloromethane; The catalyst used in step one is 4-dimethylaminopyridine; In step one, the molar ratio of (S)-2-methylaziridine, 2-(triphenylsilyl)ethane-1-sulfonyl chloride and N,N-diisopropylethylamine is 1:1.0-1.1:1.2-1.8.

[0008] Furthermore, the amount of 4-dimethylaminopyridine used is 0.02-0.1 times the molar amount of (S)-2-methylaziridine; The reaction in the first step involves adding 2-(triphenylsilyl)ethane-1-sulfonyl chloride dropwise at 0-10℃ and maintaining the temperature at 20-30℃ for 3-6 hours.

[0009] Furthermore, the post-processing in step one includes: quenching with saturated ammonium chloride aqueous solution, washing with citric acid aqueous solution, sodium bicarbonate aqueous solution and saturated brine, drying with anhydrous magnesium sulfate, and then crystallizing and purifying with a mixed solvent of n-hexane and ethyl acetate in a volume ratio of 8-12:1.

[0010] Furthermore, the reaction route for step two is as follows: ; The raw materials for step two are: (S)-2-(triphenylsilyl)ethane-1-sulfonyl-2-methylaziridine and diethylaluminum cyanide; The amount of diethylaluminum cyanide used is 1.1-1.3 equivalents of (S)-2-(triphenylsilyl)ethane-1-sulfonyl-2-methylaziridine; The solvent in step two is toluene; Step two is performed under nitrogen or argon protection.

[0011] Furthermore, in step two, the reaction conditions are as follows: diethylaluminum cyanide is added dropwise at 0-5℃, and after the addition is complete, the reaction is carried out at 35-45℃ for 6-10 hours; the reaction solution is made of 10% potassium sodium tartrate aqueous solution to break down the aluminum complex.

[0012] Furthermore, the post-processing in step two includes: extraction with ethyl acetate, drying with anhydrous sodium sulfate, and concentration followed by slurrying and recrystallization using a mixed solvent of methyl tert-butyl ether and n-heptane in a volume ratio of 1:4-6.

[0013] Furthermore, the synthetic route for step three is as follows: ; Step three uses (S)-N-(1-cyanopropan-2-yl)-2-(triphenylsilyl)ethane-1-sulfonamide as a raw material; The removal reagent in step three is tetra-n-butylammonium fluoride; The salt-forming reagent in step three is a hydrogen chloride-dioxane solution; The solvent in step three is anhydrous tetrahydrofuran; The amount of tetra-n-butylammonium fluoride used is 2.0-2.5 equivalents of (S)-N-(1-cyanopropane-2-yl)-2-(triphenylsilyl)ethane-1-sulfonamide, the reaction temperature is 40-60℃, and the reaction time is 4-8 hours.

[0014] Furthermore, in step three, after the reaction is completed, purified water is added and the tetrahydrofuran is removed by vacuum concentration. The byproduct triphenylsilane fluoride is separated by extraction with methyl tert-butyl ether. After back-extraction of the aqueous phase with 1.0M hydrochloric acid, the organic phase is washed with dichloromethane, and the combined aqueous phases are freeze-dried to obtain the crude product.

[0015] Furthermore, the post-processing in step three includes: dissolving the crude product obtained by freeze drying in anhydrous ethanol, heating to 35-45°C, adding anhydrous diethyl ether dropwise with stirring until slightly turbid, cooling in an ice-water bath to crystallize for 3-5 hours, filtering and vacuum drying to obtain pure (S)-3-aminobutyronitrile hydrochloride with an optical purity ≥99.5%ee.

[0016] Compared with the prior art, the beneficial effects of the present invention are: 1. This invention is the first to introduce 2-(triphenylsilyl)ethanesulfonyl (TPES) as a sterically hindered, highly crystalline directed protecting group into this synthetic route, constructing a chiral center through a highly regioselective ring-opening reaction of (S)-2-methylaziridine. Compared with existing enzymatic resolution methods, this method significantly improves atom economy, achieving an overall yield of over 78% in the three-step reaction, and avoids racemization and intramolecular cyclization side reactions that are prone to occur in traditional chemical reduction methods.

[0017] 2. The introduction of the TPES protecting group endows each intermediate with excellent crystallization properties. The products from steps one and two can be efficiently purified through simple crystallization or pulping and recrystallization. In step three, the target amine salt and the byproduct triphenylsilane fluoride can be completely separated using a polarity-reversed liquid-liquid extraction strategy. The entire process avoids multiple column chromatography purifications, reduces solvent consumption by more than 60%, is simple to operate, has good reproducibility, and is very suitable for industrial-scale production.

[0018] 3. The reaction temperature in each step of this invention is controlled within the range of 0-60℃, eliminating the need for high-pressure hydrogenation equipment or expensive chiral metal catalysts, significantly reducing equipment investment and production safety risks. The final product, (S)-3-aminobutyronitrile hydrochloride, is a white crystalline solid with an optical purity ≥99.5%ee. Compared to the oily products obtained by traditional methods, it has advantages such as good stability, ease of storage and measurement, and can be directly used for the synthesis of downstream DPP-4 inhibitor drugs.

[0019] 4. The β-elimination reaction is initiated by the specific attack of fluoride ions on silicon atoms, resulting in a clean and thorough deprotection process without the generation of difficult-to-separate nitrogen-containing byproducts. A simple combination of methyl tert-butyl ether extraction and acid-water back-extraction can achieve efficient separation of the target product from silicon-containing byproducts, with a product purity exceeding 99.8%, meeting the quality requirements for pharmaceutical intermediates. Attached Figure Description

[0020] Figure 1 The image shows the NMR spectrum of (S)-3-aminobutyronitrile hydrochloride prepared in Example 1 of this invention. Detailed Implementation

[0021] The technical solution of the present invention will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are merely some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0022] Example 1 Preparation of (S)-3-aminobutyronitrile hydrochloride: Step 1: ; Under nitrogen protection, (S)-2-methylaziridine (5.00 g, 1.0 eq), anhydrous dichloromethane (100 mL), N,N-diisopropylethylamine (16.98 g, 1.5 eq), and 4-dimethylaminopyridine (0.54 g, 0.05 eq) were added sequentially to the reaction flask. Stirring was started to ensure homogeneous mixing. The reaction flask was placed in an ice-water bath until the internal temperature dropped to between 0 and 5 °C. Separately, 2-(triphenylsilyl)ethane-1-sulfonyl chloride (35.58 g, 1.05 eq) was dissolved in anhydrous dichloromethane (50 mL) and transferred to a constant-pressure dropping funnel. Under vigorous stirring, the 2-(triphenylsilyl)ethane-1-sulfonyl chloride solution was slowly added dropwise to the reaction system, ensuring the reaction system temperature did not exceed 10 °C. After the addition was complete, the ice-water bath was removed, and the reaction system was allowed to naturally warm to room temperature. The reaction was then maintained at this temperature with stirring for 4.5 hours. After the reaction was complete, the reaction solution was cooled back to below 10°C, and 100 mL of saturated ammonium chloride aqueous solution was slowly added to quench the reaction. The mixture was transferred to a 500 mL separatory funnel, shaken thoroughly, and allowed to stand for separation of the lower organic phase. The aqueous phase was extracted with dichloromethane (2 × 50 mL). All organic phases were combined and washed successively with 5% citric acid aqueous solution (100 mL) to remove residual DIPEA and DMAP, followed by washing with saturated sodium bicarbonate aqueous solution (100 mL) until neutral, and finally with saturated saline solution (100 mL). The washed organic phase was transferred to an Erlenmeyer flask, and an appropriate amount of anhydrous magnesium sulfate was added for drying for 30 minutes. The desiccant was removed by suction filtration through a Buchner funnel, and the filter cake was washed with a small amount of dichloromethane (20 mL). The filtrate was transferred to a single-necked flask and concentrated under reduced pressure using a rotary evaporator to obtain a crude residue. A mixed solvent of hexane and ethyl acetate (volume ratio 10:1) (150 mL) was added to the crude residue, and the mixture was heated to reflux until completely dissolved. Heating was then stopped, and the solution was allowed to cool naturally to room temperature before being placed in a 4°C refrigerator for crystallization for 12 hours. The precipitated crystals were collected by suction filtration, and the filter cake was washed with a small amount of ice-cold washing solvent (hexane / ethyl acetate 10:1). The cake was then dried to constant weight in a vacuum drying oven to obtain 31.66 g (yield 88.69%) of the pure target product (S)-2-(triphenylsilyl)ethane-1-sulfonyl-2-methylaziridine.

[0023] Step Two: ; Add (S)-2-(triphenylsilyl)ethane-1-sulfonyl-2-methylaziridine (31.66 g, 1 eq) to the reaction flask, followed by anhydrous toluene (300 mL). Turn on the magnetic stirrer to ensure the substrate is evenly dispersed. Cool the reaction flask in an ice-water bath until the internal temperature drops to 0°C. Transfer a 1.0 M diethylaluminum cyanide toluene solution (93.2 mL, 1.2 eq) to a constant-pressure dropping funnel. Under nitrogen protection and stirring, slowly add the diethylaluminum cyanide solution dropwise. Control the internal temperature of the reaction system between 0 and 5°C. After the addition is complete, maintain stirring in the ice bath for 15 minutes to ensure homogeneous mixing. Remove the ice-water bath and place the reaction flask in an oil bath, slowly heating until the internal temperature stabilizes at 40°C. Stir continuously at this temperature for 8 hours. Cool the reaction mixture back to an ice-water bath to below 0°C. Quenching was performed by adding 250 mL of a 10% sodium potassium tartrate aqueous solution very slowly through a constant-pressure dropping funnel while stirring. The initial quenching process was accompanied by the generation of numerous bubbles and significant exothermic activity; the dropping rate had to be controlled to prevent material spillage. After the addition was complete, the ice-water bath was removed, and the mixture was stirred vigorously at room temperature for 2 hours until the aluminum complex was completely broken down, and the system transformed from an initial turbid emulsion into two clear layers: an aqueous phase and an organic phase. The mixture was transferred to a 1 L separatory funnel and allowed to stand to separate the organic layer. The aqueous phase was then extracted twice with ethyl acetate (2 × 200 mL). All organic layers were combined and washed successively with water (150 mL) and saturated brine (150 mL). The organic layer was transferred to an Erlenmeyer flask and dried for 30 minutes with anhydrous sodium sulfate (30 g). The drying agent was removed by filtration through a Buchner funnel, and the filtrate was concentrated under reduced pressure on a rotary evaporator until most of the solvent was removed, yielding a viscous, oily crude product. Add methyl tert-butyl ether (MTBE, 30 mL) to the crude product and heat to 45 °C while stirring until completely dissolved. Then, under rapid stirring, slowly add n-heptane (150 mL, MTBE:Heptane = 1:5 by volume). A white solid gradually precipitates during the addition. After the addition is complete, slowly cool the suspension to room temperature and continue to slurry in an ice bath at 0 °C for 2 hours. Collect the precipitated solid by vacuum filtration, wash the filter cake with a small amount of cold n-heptane, and dry it in a vacuum drying oven for 12 hours to obtain 30.09 g of pure target product (yield 89.14%) (S)-N-(1-cyanopropane-2-yl)-2-(triphenylsilyl)ethane-1-sulfonamide.

[0024] Step 3: ; Under a stable argon flow and at room temperature, the main raw material (S)-N-(1-cyanopropane-2-yl)-2-(triphenylsilyl)ethane-1-sulfonamide (30.09 g, 1 eq) was added to a reaction flask, followed by anhydrous tetrahydrofuran (200.0 mL). Stirring was initiated until the mixture was uniformly dispersed. The reaction flask was placed in an ice-water bath to cool. When the internal temperature dropped to between 0-5°C, a 1.0 M tetrabutylammonium fluoride tetrahydrofuran solution (152.3 mL, 2.2 eq) was slowly added dropwise through a constant-pressure dropping funnel. The dropping rate was controlled to maintain the internal temperature below 10°C. After the addition was complete, the solution gradually turned slightly yellow. The ice-water bath was removed, and a temperature-controlled oil bath was used instead. The reaction solution was slowly heated until the internal temperature was constant at 50°C. At this temperature, the reaction solution was continuously and vigorously stirred for 6 hours. A small amount of gas was observed to be generated during the reaction. The reaction solution was removed from the oil bath and cooled to room temperature. Salt formation was initiated by slowly adding 34.6 mL of 4.0 M hydrogen chloride-dioxane solution (2.0 eq) under ice bath cooling and vigorous stirring for 30 minutes. Subsequently, purified water (150.0 mL) was slowly added to the system, and the mixture was transferred to a single-necked flask. The mixture was concentrated under reduced pressure using a rotary evaporator at 35°C in a water bath to remove tetrahydrofuran and dioxane to the greatest extent possible. The remaining aqueous phase mixture was transferred to a 1000 mL separatory funnel, and 150 mL of methyl tert-butyl ether was added for extraction to separate the byproduct triphenylsilane fluoride and other weakly polar organic impurities. The organic and aqueous phases were separated. To prevent product loss, the combined MTBE organic phase was back-extracted with 50 mL of 1.0 M hydrochloric acid aqueous solution. All aqueous phases containing the product were combined. The combined aqueous phases were further washed with 100 mL of dichloromethane to thoroughly remove any remaining trace aromatic and siliceous impurities. The final aqueous phase was freeze-dried for 48 hours to obtain a slightly yellow crude solid of (S)-3-aminobutyronitrile hydrochloride. The freeze-dried crude product was placed in a 250 mL round-bottom flask, and anhydrous ethanol (approximately 60 mL) was added. The mixture was heated to 40 °C to completely dissolve the product. Under constant temperature stirring, anhydrous diethyl ether (approximately 120 mL) was added dropwise very slowly until a persistent slight turbidity appeared. The addition of diethyl ether was stopped, the heating was removed, and the system was allowed to cool naturally to room temperature. Then, it was transferred to an ice-water bath (0 °C) for 4 hours to allow crystallization. A large number of snow-white needle-like crystals were observed to precipitate. The crystals were filtered under reduced pressure using a Buchner funnel, and the filter cake was washed with a small amount of cold ethanol / diethyl ether (1:3) mixed solvent. The crystals were dried in a vacuum drying oven for 12 hours to obtain 7.09 g of (S)-3-aminobutyronitrile hydrochloride (yield 85.0%). The NMR spectrum is shown below. Figure 1 As shown, the optical purity is ≥99.5%ee.

[0025] Example 2 The preparation of (S)-3-aminobutyronitrile hydrochloride was carried out according to the steps of Example 1, except that the amount of 4-dimethylaminopyridine (DMAP) used in step 1 was replaced from 0.05 eq to 0.02 eq, the yield of step 1 was 87.6%, and the rest remained the same as in Example 1.

[0026] Example 3 The preparation of (S)-3-aminobutyronitrile hydrochloride was carried out according to the steps of Example 1, except that the amount of diethylaluminum cyanide used in step 2 was replaced from 1.2 eq to 1.1 eq, the yield of step 2 was 88.1%, and the rest was the same as in Example 1.

[0027] Example 4 The preparation of (S)-3-aminobutyronitrile hydrochloride was carried out according to the steps of Example 1, except that the amount of tetra-n-butylammonium fluoride (TBAF) used in step 3 was replaced from 2.2 eq to 2.0 eq, the yield of step 3 was 83.5%, and the rest remained the same as in Example 1.

[0028] Comparative Example 1 The preparation of (S)-3-aminobutyronitrile hydrochloride was carried out according to the steps of Example 1, except that the base used in step 1 was replaced with triethylamine (TEA) instead of N,N-diisopropylethylamine (DIPEA). The yield of step 1 was 80.2%, and the rest was the same as in Example 1.

[0029] Comparative Example 2 The preparation of (S)-3-aminobutyronitrile hydrochloride was carried out according to the steps of Example 1, except that the catalyst used in step 1 was replaced with 4-dimethylaminopyridine (DMAP) and no catalyst was added. The yield of step 1 was 76.5%, and the rest was the same as in Example 1.

[0030] Comparative Example 3 The preparation of (S)-3-aminobutyronitrile hydrochloride was carried out according to the steps of Example 1, except that the amount of 2-(triphenylsilyl)ethane-1-sulfonyl chloride in step one was replaced with 1.00 eq instead of 1.05 eq. The yield of step one was 84.0%, and the rest was the same as in Example 1.

[0031] Comparative Example 4 The preparation of (S)-3-aminobutyronitrile hydrochloride follows the steps of Example 1, except that the amount of diethylaluminum dicyanide added in step 2 is replaced with 1.1 eq instead of 1.2 eq. The yield of step 2 is 85.5%, and the rest is the same as in Example 1.

[0032] The examples follow the route of Example 1: first, substrate sulfonation protection is completed under DMAP catalysis and DIPEA as a base (step one); then, a cyano group is introduced by selective ring opening using diethylaluminum cyanide (step two); finally, deprotection is achieved by TBAF and salt formation with HCl to obtain (S)-3-aminobutyronitrile hydrochloride (step three). Examples 2-4 each involve minor parameter substitutions at only one point, while the other conditions remain unchanged. Comparative Examples 1-4 also use Example 1 as a reference, but comparisons are made on single characteristics such as base, catalyst, and key feed equivalence. The results show that the yield of the corresponding steps decreases, indicating that the base system, catalytic promotion, and reasonable equivalence control selected in Example 1 significantly contribute to improving reaction conversion and yield, and ensuring the overall process effect.

[0033] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for preparing a (S)-3-aminobutyronitrile hydrochloride compound, characterized in that, The preparation method uses (S)-2-methylaziridine and 2-(triphenylsilyl)ethane-1-sulfonyl chloride as starting materials, and prepares (S)-3-aminobutyronitrile hydrochloride through a three-step reaction of adding a protecting group, selective ring opening, deprotection and salt formation. Step 1, the product in the upper protecting group is: (S)-2-(triphenylsilyl)ethane-1-sulfonyl-2-methylaziridine; Step two, the selectively ring-opening product is: (S)-N-(1-cyanopropan-2-yl)-2-(triphenylsilyl)ethane-1-sulfonamide; The structure of (S)-2-(triphenylsilyl)ethane-1-sulfonyl-2-methylaziridine is as follows: ; The structure of the (S)-N-(1-cyanopropan-2-yl)-2-(triphenylsilyl)ethane-1-sulfonamide is as follows: .

2. The method for preparing a (S)-3-aminobutyronitrile hydrochloride compound according to claim 1, characterized in that, The synthetic route for step one is as follows: ； In step one, N,N-diisopropylethylamine is used as a bound acid. The solvent used in step one is anhydrous dichloromethane; The catalyst used in step one is 4-dimethylaminopyridine; In step one, the molar ratio of (S)-2-methylaziridine, 2-(triphenylsilyl)ethane-1-sulfonyl chloride and N,N-diisopropylethylamine is 1:1.0-1.1:1.2-1.

8.

3. The method for preparing a (S)-3-aminobutyronitrile hydrochloride compound according to claim 2, characterized in that, The amount of 4-dimethylaminopyridine used is 0.02-0.1 times the molar amount of (S)-2-methylaziridine; The reaction temperature in step one is 0-10℃ for the dropwise addition of 2-(triphenylsilyl)ethane-1-sulfonyl chloride, and the reaction is maintained at 20-30℃ for 3-6 hours.

4. The method for preparing a (S)-3-aminobutyronitrile hydrochloride compound according to claim 2, characterized in that, The post-processing in step one includes: quenching with saturated ammonium chloride aqueous solution, washing with citric acid aqueous solution, sodium bicarbonate aqueous solution and saturated brine, drying with anhydrous magnesium sulfate, and then crystallizing and purifying with a mixed solvent of n-hexane and ethyl acetate in a volume ratio of 8-12:

1.

5. The method for preparing a (S)-3-aminobutyronitrile hydrochloride compound according to claim 1, characterized in that, The reaction route for step two is as follows: ； The raw materials for step two are: (S)-2-(triphenylsilyl)ethane-1-sulfonyl-2-methylaziridine and diethylaluminum cyanide; The amount of diethylaluminum cyanide used is 1.1-1.3 equivalents of (S)-2-(triphenylsilyl)ethane-1-sulfonyl-2-methylaziridine; The solvent in step two is toluene; Step two is performed under nitrogen or argon protection.

6. The method for preparing a (S)-3-aminobutyronitrile hydrochloride compound according to claim 5, characterized in that, In step two, the reaction conditions are as follows: diethylaluminum cyanide is added dropwise at 0-5℃, and after the addition is complete, the reaction is carried out at 35-45℃ for 6-10 hours; the reaction solution is made of 10% potassium sodium tartrate aqueous solution to break down the aluminum complex.

7. The method for preparing a (S)-3-aminobutyronitrile hydrochloride compound according to claim 6, characterized in that, The post-processing in step two includes: extraction with ethyl acetate, drying with anhydrous sodium sulfate, concentration, and recrystallization using a mixed solvent of methyl tert-butyl ether and n-heptane in a volume ratio of 1:4-6.

8. The method for preparing a (S)-3-aminobutyronitrile hydrochloride compound according to claim 1, characterized in that, The synthetic route for step three is as follows: ； Step three uses (S)-N-(1-cyanopropan-2-yl)-2-(triphenylsilyl)ethane-1-sulfonamide as a raw material; The removal reagent in step three is tetra-n-butylammonium fluoride; The salt-forming reagent in step three is a hydrogen chloride-dioxane solution; The solvent in step three is anhydrous tetrahydrofuran; The amount of tetra-n-butylammonium fluoride used is 2.0-2.5 equivalents of (S)-N-(1-cyanopropane-2-yl)-2-(triphenylsilyl)ethane-1-sulfonamide, the reaction temperature is 40-60℃, and the reaction time is 4-8 hours.

9. The method for preparing a (S)-3-aminobutyronitrile hydrochloride compound according to claim 8, characterized in that, In step three, after the reaction is complete, purified water is added and the tetrahydrofuran is removed by vacuum concentration. The byproduct triphenylsilane fluoride is separated by extraction with methyl tert-butyl ether. The aqueous phase is back-extracted with 1.0M hydrochloric acid, and the organic phase is washed with dichloromethane. The combined aqueous phases are freeze-dried to obtain the crude product.

10. The method for preparing a (S)-3-aminobutyronitrile hydrochloride compound according to claim 9, characterized in that, The post-processing in step three includes: dissolving the crude product obtained by freeze drying in anhydrous ethanol, heating to 35-45℃, adding anhydrous diethyl ether dropwise with stirring until slightly turbid, cooling in an ice-water bath to crystallize for 3-5 hours, filtering and vacuum drying to obtain pure (S)-3-aminobutyronitrile hydrochloride with an optical purity ≥99.5%ee.

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