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Synthesis technology of rebamipide

A synthesis process, the technology of rebamipide, which is applied in the field of synthesis technology of rebamipide, can solve the problems of low content of rebamipide, high production cost, difficult removal of impurities, etc., and achieves simple synthesis conditions and high yield. The effect of high and low production cost

Inactive Publication Date: 2018-07-13
千辉药业(安徽)有限责任公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Rebamipide has a variety of preparation and synthesis methods, but most of them have the disadvantages that the content of rebamipide in the obtained finished product is low, and some impurities are difficult to remove. The acylation reaction process in the synthesis has strict requirements on the environmental conditions. These Raise the cost of production

Method used

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  • Synthesis technology of rebamipide
  • Synthesis technology of rebamipide
  • Synthesis technology of rebamipide

Examples

Experimental program
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Effect test

Embodiment 1

[0027] A kind of synthetic technique of the synthetic technique of rebamipide, such as figure 1 As shown, the specific synthesis process is as follows:

[0028] (1) Add 1L of concentrated ammonia water into the reaction vessel, then drop 1.843kg of 4-chlorobenzoyl chloride into it dropwise, control the reaction temperature within 30°C, and react by mechanical stirring for 4.5h to obtain 4-chlorobenzoyl chloride ;

[0029] (2) under the protection of nitrogen, add 1L anhydrous tetrahydrofuran and 72g magnesium chips in the container, and add a few drops of methyl iodide, be warming up to 80 ℃, add 695.3g4-bromomethylquinolone dropwise after stirring and dissolving, After the dropwise addition was completed, react at a constant temperature for 10 hours. After cooling down to room temperature, 101.26 g of formic acid was added dropwise. After the dropwise addition was complete, the temperature was raised to 70°C for 5 hours.

[0030] (3) 930g of product 1, 383.5g of sodium cyan...

Embodiment 2

[0034] A synthetic process of the synthetic process of rebamipide, the specific synthetic process is as follows:

[0035] (1) Add 1L of ammonia water into the reaction vessel, then drop 1.935kg of 4-chlorobenzoyl chloride into it dropwise, control the reaction temperature within 30°C, and react by mechanical stirring for 4.5h to obtain 4-chlorobenzoyl chloride;

[0036] (2) under the protection of nitrogen, add 1L anhydrous tetrahydrofuran and 72g magnesium chips in the container, and add a few drops of methyl iodide, be warming up to 80 ℃, add 704.9g4-bromomethylquinolone dropwise after stirring and dissolving, After the dropwise addition was completed, react at a constant temperature for 10 hours. After cooling down to room temperature, 115.07 g of formic acid was added dropwise. After the dropwise addition was complete, the temperature was raised to 70°C for 5 hours.

[0037] (3) 930g of product 1, 393.25g of sodium cyanate and 396.9g of sulfuric acid solution were added to...

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Abstract

The invention discloses a synthesis technology of rebamipide. A specific synthesis process comprises the following steps: adding ammonia water into a reaction container; then dropwise adding 4-chlorobenzoyl chloride into the reaction container to obtain 4-chlorobenzamide; after carrying out Grignard reaction, reacting with formic acid to prepare a product 1; carrying out addition reaction on the product 1 to prepare a product 2; after carrying out chlorination on the product 2, taking the product 2 and the 4-chlorobenzamide to react to obtain a product 3; adding the product 3 into the reactioncontainer and adding a sulfuric acid solution with the mass percent of 60 percent into the reaction container; heating to 80 DEG C and stirring to react for 3h to obtain a product 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinone-4]propionic acid. In a synthesis process, the rebamipide is prepared through the Grignard reaction, nucleophilic addition and substitution reaction; the production cost is low and the yield of the product is high; synthesis conditions are simple and the synthesis technology can be applicable to large-scale production.

Description

technical field [0001] The invention belongs to the field of pharmacy and relates to a synthesis process of rebamipide. Background technique [0002] Rebamipide, the chemical name is 2-(4-chlorobenzamido)-3-[2(1H)-quinolinone-4]propionic acid, rebamipide is an active new generation of gastric mucosal protection It can improve the histological healing quality of gastric ulcer and reduce the recurrence of ulcer. It has a good effect on the treatment of gastric mucosal damage caused by factors such as non-steroidal anti-inflammatory drugs (NSAIDs) and alcohol. It still has a good curative effect on gastric mucosal lesions, and it is the only gastric mucosal protective agent that can increase PG synthesis and scavenge and inhibit free radicals, and has high clinical application value. [0003] Rebamipide has a variety of preparation and synthesis methods, but most of them have the disadvantages that the content of rebamipide in the obtained finished product is low, and some imp...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D215/227
CPCC07D215/227
Inventor 杨会来毛杰孙学喜
Owner 千辉药业(安徽)有限责任公司
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