Synthetic method of parecoxib sodium impurity

A technology for parecoxib sodium and a synthesis method is applied in the field of chemical pharmacy to achieve the effects of cheap raw materials, improved quality and simple operation

Active Publication Date: 2015-04-29
CHENGDU CLIMB PHARMA TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

After searching, there is no bibliographical report about the synthesis of this impurity, therefore, it is of great practical significance to provide a synthetic method of parecoxib sodium impurity H for the preparation of impurity standard

Method used

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  • Synthetic method of parecoxib sodium impurity
  • Synthetic method of parecoxib sodium impurity
  • Synthetic method of parecoxib sodium impurity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Embodiment 1: the synthetic method of parecoxib sodium impurity 1 N-[[3-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonyl]propionamide

[0022] Add 10g of 5-methyl-3,4-diphenylisoxazole, 7g of zinc chloride, and 20g of chlorosulfonic acid into the reaction flask, and react at 60°C for 2 hours. After the reaction is completed, add dropwise to 100g of ice water, Filtrate, dissolve the filter cake in 10g of ethyl acetate, add 50g of petroleum ether to crystallize, filter, and concentrate the filtrate to dryness under reduced pressure. After the concentration is complete, add 200g of petroleum ether, filter, and dry under normal pressure at 50-60°C for about 8 hours to obtain N- [3-(5-Methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonyl chloride 5.42 g, yield 38.2%.

[0023] Add 5g of the above N-[3-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonyl chloride and 200g of dichloromethane into the reaction flask, after the solid dissolves, add dropwise to 250g of ammonia water , reacted f...

Embodiment 2

[0028] Embodiment 2: the synthetic method of parecoxib sodium impurity 1 N-[[3-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonyl]propionamide

[0029] Add 10g of 5-methyl-3,4-diphenylisoxazole, 5g of zinc chloride, and 10g of chlorosulfonic acid into the reaction flask, and react at 60°C for 2 hours. After the reaction is completed, add dropwise to 100g of ice water, Filtrate, dissolve the filter cake in 10g of ethyl acetate, add 50g of petroleum ether to crystallize, filter, and concentrate the filtrate to dryness under reduced pressure. After the concentration is complete, add 200g of petroleum ether, filter, and dry under normal pressure at 50-60°C for about 8 hours to obtain N- [3-(5-Methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonyl chloride 5.13 g, yield 36.1%.

[0030] Add 5g of the above N-[3-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonyl chloride and 200g of dichloromethane into the reaction flask, after the solid dissolves, add dropwise to 200g of ammonia water , reacted f...

Embodiment 3

[0032] Embodiment 3: the synthetic method of parecoxib sodium impurity 1 N-[[3-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonyl]propionamide:

[0033] Add 10g of 5-methyl-3,4-diphenylisoxazole, 10g of zinc chloride, and 50g of chlorosulfonic acid into the reaction flask, and react at 60°C for 2 hours. After the reaction is completed, add dropwise to 100g of ice water, Filtrate, dissolve the filter cake in 10g of ethyl acetate, add 50g of petroleum ether to crystallize, filter, and concentrate the filtrate to dryness under reduced pressure. After the concentration is complete, add 200g of petroleum ether, filter, and dry under normal pressure at 50-60°C for about 8 hours to obtain N- [3-(5-Methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonyl chloride 5.54 g, yield 39.0%.

[0034] Add 5g of the above N-[3-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonyl chloride and 200g of dichloromethane into the reaction flask, after the solid dissolves, add dropwise to 350g of ammonia water , reacted...

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Abstract

The invention discloses a synthetic method of a parecoxib sodium impurity, namely N-[[3-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonyl]propanamide, belonging to the technical field of chemical pharmacy; the parecoxib sodium impurity is obtained by carrying out sulfonation reaction, amination reaction and propionylation reaction by taking 5-methyl-3,4-diphenyl isoxazole as the raw material; the synthesized high-purity parecoxib sodium impurity can be used as an impurity standard sample in detection and analysis of parecoxib sodium finished products; therefore, the accurate positioning property and the qualitative diagnosis to impurities in detection and analysis of parecoxib sodium finished products are increased; control of the impurity is strengthened easily, so that the quality of the parecoxib sodium finished products is increased; the synthetic method disclosed by the invention is cheap and available in raw materials and simple to operate; the yield of the prepared parecoxib sodium impurity is 85+/-5%; and the HPLC (High Performance Liquid Chromatography) purity is more than or equal to 98%.

Description

technical field [0001] The invention belongs to the technical field of chemical pharmacy, in particular to a parecoxib sodium impurity I N-[[3-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonyl]propane Synthesis of amides. Background technique [0002] The inflammatory response after noxious stimuli such as surgery and trauma can lead to the release of inflammatory mediators and pain-causing substances. In addition to directly causing pain, they can also cause blood vessels to dilate, tissue edema, increase the sensitivity of effector receptors, and reduce the pain threshold. This results in peripheral hyperalgesia. Selective COX-2 inhibitors can effectively inhibit the expression of peripheral COX-2 and reduce the synthesis of peripheral prostaglandins, thereby exerting analgesic and anti-inflammatory effects. At the same time, they can inhibit the expression of central COX-2, inhibit the synthesis of central prostaglandins and inhibit pain hypersensitivity Give full play to...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D261/08
CPCC07D261/08
Inventor 蒋明勇刘芍利叶丁林蓉莹
Owner CHENGDU CLIMB PHARMA TECH
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