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Method for synthesizing ranolazine

A synthesis method and a technology of ranolazine are applied in the synthesis field of anti-angina pectoris drug ranolazine, can solve the problems of difficulty in industrialized production, low yield, complicated operation and the like, and achieve the effects of good quality, high yield and simplified operation steps

Inactive Publication Date: 2009-09-30
FUJIAN TIANQUAN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Method 1 In the process of preparing the intermediate N-(2,6-dimethylphenyl)-2-(1-piperazinyl)acetamide, it is generally purified with dichloromethane, which requires extraction and removal of dichloromethane. The steps of methyl chloride moisture are cumbersome to operate and require liquid separation equipment and moisture absorption facilities
In addition, in the prior art, silica gel columns are often used for the purification of ranolazine, and industrial production is relatively difficult. Ranolazine is also recrystallized with a mixed solvent, but the yield is low

Method used

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  • Method for synthesizing ranolazine
  • Method for synthesizing ranolazine
  • Method for synthesizing ranolazine

Examples

Experimental program
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Embodiment 1

[0028] 1) Preparation of N-(2,6-dimethylphenyl)-2-(1-piperazinyl)acetamide

[0029] Add 60g of N-(2,6-dimethylphenyl) chloroacetamide, 103.2g of anhydrous piperazine and 600ml of absolute ethanol in the reaction flask, and stir the reaction mixture under reflux for 3hr. After the reaction is completed, cool to room temperature and add ammonia water Adjust the pH value to 9, add 500ml of ethyl acetate after concentrating under reduced pressure to recover the solvent, stir to dissolve, filter, concentrate and recover the solvent under reduced pressure to dryness, then add 750ml of anhydrous ether, stir to complete the precipitation, filter, take the precipitate and dry it to obtain white solid product. mp: 109-111°C.

[0030] 2) preparation of ranolazine crude product

[0031] Add 60g N-(2,6-dimethylphenyl)-1-piperazine acetamide and 48g 1-(2-methoxyphenoxy group)-2,3-propylene oxide in the reaction flask, and then After adding 600 ml of absolute ethanol, the reaction mixture...

Embodiment 2

[0036] 1) Preparation of N-(2,6-dimethylphenyl)-2-(1-piperazinyl)acetamide

[0037] Add 66g of N-(2,6-dimethylphenyl) chloroacetamide, 90g of anhydrous piperazine and 600ml of absolute ethanol in the reaction flask, stir the reaction mixture and reflux for 5hr, after the reaction is completed, cool to room temperature, add ammonia water to adjust The pH value is 10, add 500ml of ethyl acetate after concentrating under reduced pressure to recover the solvent, stir to dissolve, filter, concentrate under reduced pressure and recover the solvent to dryness, then add 750ml of anhydrous ether, stir to complete the precipitation, filter, take the precipitate and dry to obtain a white solid product. mp: 109-111°C.

[0038] 2) preparation of ranolazine crude product

[0039] Add 72g N-(2,6-dimethylphenyl)-1-piperazine acetamide and 36g 1-(2-methoxyphenoxy group)-2,3-propylene oxide in the reaction flask, and then 600ml of absolute ethanol was added, and the reaction mixture was stir...

Embodiment 3

[0044] 1) Preparation of N-(2,6-dimethylphenyl)-2-(1-piperazinyl)acetamide

[0045] Add 54g of N-(2,6-dimethylphenyl) chloroacetamide, 108g of anhydrous piperazine and 600ml of absolute ethanol in the reaction flask, stir the reaction mixture and reflux for 4hr, after the reaction is completed, cool to room temperature, add ammonia water to adjust The pH value is 9, add 500ml of ethyl acetate after concentrating under reduced pressure to recover the solvent, stir to dissolve, filter, concentrate under reduced pressure and recover the solvent to dryness, then add 750ml of anhydrous ether, stir to complete the precipitation, filter, take the precipitate and dry to obtain a white solid product. mp: 109-111°C.

[0046] 2) preparation of ranolazine crude product

[0047]Add 48g N-(2,6-dimethylphenyl)-1-piperazine acetamide and 60g 1-(2-methoxyphenoxy group)-2,3-propylene oxide in the reaction flask, and then 600ml of absolute ethanol was added, and the reaction mixture was stirr...

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Abstract

The invention discloses a method for synthesizing an anti-angina medicament, namely ranolazine, which comprises the following steps that: N-(2,6-dimethylphenyl)chloracetamide is taken as an initial raw material and is condensed with piperazidine, and then the aminolysis reaction of the obtained product and 1-(2-methoxyphenoxyl)-2,3-propylene oxide is performed to obtain a product, namely the ranolazine. During the preparation of an intermediate, namely N-(2,6-dimethylphenyl)-2-(1-piperazinyl)acetamide, the invention improves an operation method, simplifies operation steps, and improves the yield of products.

Description

technical field [0001] The invention relates to a synthesis method of ranolazine, an antiangina medicine. Background technique [0002] Ranolazine is a piperazine derivative with the chemical name N-(2,6-dimethylphenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)propyl] -1-Piperazine acetamide is a new anti-angina drug developed and created by Syntex Corporation of the United States. [0003] According to literature reports, according to the order of the upper piperazine ring, there are mainly the following two methods: [0004] method 1: [0005] [0006] Method 2: [0007] [0008] The quality of the intermediate obtained by method 1 is easier to control, and the operability is better than that of method 2, and method 1 is more suitable for industrialization, and this method is generally used for the synthesis of ranolazine. Method 1 In the process of preparing the intermediate N-(2,6-dimethylphenyl)-2-(1-piperazinyl)acetamide, it is generally purified with dichloromethane...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D295/15A61P9/10
Inventor 邓志平邓志明邓志清
Owner FUJIAN TIANQUAN PHARMA
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