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Preparation method of amisulpride

A technology of amisulpride and compounds, applied in the field of pharmaceutical chemical synthesis, can solve problems such as cumbersomeness, unfavorable industrial production, and long reaction time, and achieve the effects of high reaction selectivity, high yield of target products, and short preparation cycle

Active Publication Date: 2019-12-17
山东安弘制药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In this invention, 2-methoxy-4-amino-5-ethanesulfonylbenzoic acid is first reacted with thionyl chloride to obtain an acid chloride, and then reacted with a lower alcohol to obtain a lower alcohol ester, which is relatively cumbersome, and the involved esterification and The reaction time of the two-step condensation operation is long, which is not conducive to industrial production

Method used

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  • Preparation method of amisulpride
  • Preparation method of amisulpride
  • Preparation method of amisulpride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] A preparation method of amisulpride, comprising the steps of:

[0041] (1) Add 300g of dichloromethane and 50g of 2-methoxy-4-amino-5-ethanesulfonylbenzoic acid (II) into the reaction flask, stir evenly, and add 2.5g of N,N-dimethylformamide , add 24.1g of thionyl chloride dropwise at a temperature of 20-25°C, raise the temperature to 35-40°C after the dropwise addition, and reflux for 4 hours to obtain 2-methoxy-4-amino-5-ethanesulfonylbenzyl The reaction liquid of acyl chloride (III); The reaction liquid directly carries out the next step reaction without processing;

[0042] (2) The temperature of the reaction solution obtained in step (1) is lowered to 20-25°C, and the temperature is controlled at 20-25°C, and a mixed solution of 49.5g of N-ethyl-2-aminomethylpyrrolidine (IV) and 100g of dichloromethane is added dropwise After completion of the dropwise addition, the temperature was raised to 35-40°C for 4 hours, and the TLC test was qualified; the obtained reactio...

Embodiment 2

[0046] A preparation method of amisulpride, comprising the steps of:

[0047](1) Add 300g of dichloromethane and 50g of 2-methoxy-4-amino-5-ethanesulfonylbenzoic acid (II) into the reaction flask, stir well, and add 2.5g of N,N-dimethylformamide , add 24.1g of thionyl chloride dropwise at a temperature of 20-25°C, raise the temperature to 35-40°C after the dropwise addition, and reflux for 6 hours to obtain 2-methoxy-4-amino-5-ethanesulfonylbenzyl The reaction liquid of acyl chloride (III); The reaction liquid directly carries out the next step reaction without processing;

[0048] (2) The temperature of the reaction solution obtained in step (1) was lowered to 20-25°C, and the temperature was controlled at 20-25°C, and a mixed solution of 61.9g N-ethyl-2-aminomethylpyrrolidine (IV) and 100g dichloromethane was added dropwise , the dropwise addition was completed, and the heat preservation was raised to 35-40° C. for 5 hours, and the TLC test was qualified; the obtained react...

Embodiment 3

[0050] A preparation method of amisulpride, comprising the steps of:

[0051] (1) Add 300g of dichloromethane and 50g of 2-methoxy-4-amino-5-ethanesulfonylbenzoic acid (II) into the reaction flask, stir well, and add 2.5g of N,N-dimethylformamide , add 24.1g of thionyl chloride dropwise at a temperature of 20-25°C, raise the temperature to 35-40°C after the dropwise addition, and reflux for 8 hours to obtain 2-methoxy-4-amino-5-ethanesulfonylbenzyl The reaction liquid of acyl chloride (III); The reaction liquid directly carries out the next step reaction without processing;

[0052] (2) The temperature of the reaction solution obtained in step (1) was lowered to 20-25°C, and a mixed solution of 74.3g of N-ethyl-2-aminomethylpyrrolidine (IV) and 100g of dichloromethane was added dropwise at a temperature of 20-25°C , the dropwise addition was completed, and the temperature was raised to 35-40°C for 6 hours, and the TLC test was qualified; the obtained reaction solution was was...

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Abstract

The invention provides a preparation method of amisulpride. The preparation method comprises the following steps: with 2-methoxy-4-amino-5-ethylsulfonyl benzoic acid and thionyl chloride as raw materials, carrying out an acylation reaction to obtain 2-methoxy-4-amino-5-ethylsulfonyl benzoyl chloride; and then, subjecting 2-methoxy-4-amino-5-ethylsulfonyl benzoyl chloride and N-ethyl-2-aminomethylpyrrolidine to an amidation reaction on to obtain amisulpride. The preparation method has the following advantages: raw materials are easy to obtain; highly toxic products are not used; the preparation method is simple; preparation period is short; side reactions are few; the yield and purity of the target product are high; and the target product has market competitiveness.

Description

technical field [0001] The invention relates to a preparation method of amisulpride, which belongs to the field of pharmaceutical chemical synthesis. Background technique [0002] Amisulpride is a white or nearly white crystalline powder chemical with the chemical name 4-amino-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5- (Ethylsulfonyl)-2-methoxybenzamide has a structural formula as shown in Formula I below. Amisulpride is an antipsychotic drug, mainly used clinically to treat schizophrenia. [0003] [0004] Existing reports about the preparation method of amisulpride in the prior art, such as: [0005] Chinese patent document CN102807516A discloses an intermediate of amisulpride and a preparation method thereof and a method for preparing amisulpride using the intermediate, comprising: 4-amino-2-methoxyl-5-ethylsulpride Acyl benzoic acid and di-tert-butyl dicarbonate react to prepare the intermediate of amisulpride; the intermediate of amisulpride is condensed with N-ethyl-2...

Claims

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Application Information

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IPC IPC(8): C07D207/09
CPCC07D207/09
Inventor 周臣生刘朝建刘德强张博王本乾王吉忠朱成峰李涛康升旺
Owner 山东安弘制药有限公司
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