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Synthesis method for parecoxib sodium impurity

A technology of parecoxib sodium and a synthesis method, which is applied in the field of chemical pharmacy to achieve the effects of cheap raw materials, improved quality, and improved accurate positioning and characterization

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

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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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  • Synthesis method for parecoxib sodium impurity
  • Synthesis method for parecoxib sodium impurity
  • Synthesis method for parecoxib sodium impurity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Example 1: A parecoxib sodium impurity J(4-N-propionyl[5-methyl-3-(3-N-propionylphenylsulfonamide)-1,2-oxazole-4- base] benzenesulfonamide) synthetic method

[0024] Add 5g of 5-methyl-3,4-diphenylisoxazole, 20g of dichloromethane, and 70g of chlorosulfonic acid into the reaction flask, reflux for 16 hours, add the reaction solution dropwise to 70g of water, 20g of dichloromethane Extract, concentrate to dryness, add 20g ethyl acetate to crystallize for 1.5 hours, filter to get 4-[5-methyl-3-(3-phenylsulfonyl chloride)-1,2-oxazol-4-yl]benzenesulfonyl chloride 6.88g, yield 74.9%.

[0025] Add 5 g of the above solid and 20 g of dichloromethane into the reaction flask. After the solid dissolves, add dropwise to 20 g of ammonia water, react for 4 hours, concentrate to dryness under reduced pressure, add 15 g of ethanol to reflux for beating, cool to room temperature, and filter to obtain 4-[ 3.76 g of 5-methyl-3-(3-phenylsulfonamide)-1,2-oxazol-4-yl]benzenesulfonamide, yi...

Embodiment 2

[0030] Example 2: A parecoxib sodium impurity J(4-N-propionyl[5-methyl-3-(3-N-propionylphenylsulfonamide)-1,2-oxazole-4- base] benzenesulfonamide) synthetic method

[0031] Add 5g of 5-methyl-3,4-diphenylisoxazole, 20g of dichloromethane, and 100g of chlorosulfonic acid into the reaction flask, reflux for 18 hours, add the reaction solution dropwise to 80g of water, 20g of dichloromethane Extract, concentrate to dryness, add 12g ethyl acetate to crystallize for 2 hours, filter to get 4-[5-methyl-3-(3-phenylsulfonyl chloride)-1,2-oxazol-4-yl]benzenesulfonyl chloride 7.12g, yield 77.5%.

[0032] Add 5 g of the above solid and 20 g of dichloromethane into the reaction flask. After the solid dissolves, add it dropwise to 15 g of ammonia water, react for 3 hours, concentrate to dryness under reduced pressure, add 15 g of ethanol to reflux for beating, cool to room temperature, and filter to obtain 4-[ 3.60 g of 5-methyl-3-(3-phenylsulfonamide)-1,2-oxazol-4-yl]benzenesulfonamide, ...

Embodiment 3

[0034] Example 3: A parecoxib sodium impurity J(4-N-propionyl[5-methyl-3-(3-N-propionylphenylsulfonamide)-1,2-oxazole-4- base] benzenesulfonamide) synthetic method

[0035] Add 3g of 5-methyl-3,4-diphenylisoxazole, 12g of dichloromethane, and 48g of chlorosulfonic acid into the reaction flask, reflux for 14 hours, and add the reaction solution dropwise to 50g of water, 12g of dichloromethane Extract, concentrate to dryness, add 12g ethyl acetate to crystallize for 2 hours, filter to get 4-[5-methyl-3-(3-phenylsulfonyl chloride)-1,2-oxazol-4-yl]benzenesulfonyl chloride 4.10 g, yield 74.4%.

[0036] Add 4g of the above solid and 16g of dichloromethane into the reaction flask. After the solid is dissolved, add it dropwise to 20g of ammonia water, react for 5 hours, concentrate to dryness under reduced pressure, add 12g of ethanol to reflux for beating, cool to room temperature, and filter to obtain 4-[ 3.18 g of 5-methyl-3-(3-phenylsulfonamide)-1,2-oxazol-4-yl]benzenesulfonamid...

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Abstract

The invention disclose a synthesis method for a parecoxib sodium impurity namely 4-N-propionyl[5-methyl-3(3-N-propionyl phenyl sulfonamide)-1,2-oxazole-4-group] benzenesulfonamide and belongs to the technical field of chemical pharmacy. According to the synthesis method, 5-methyl-3,4-diphenyl isoxazole is used as raw material, sulfonation reaction, aminating reaction and propionylation reaction are performed so as to obtain the parecoxib sodium impurity, and the synthesized high-purity parecoxib sodium impurity can be used as a standard impurity for detection analysis of a parecoxib sodium finished product, so that accurate positioning and quantification of the parecoxib sodium finished product detection analysis to the impurity are improved, control over the impurity is strengthened, and the quality of the parecoxib sodium finished product is improved. The method provided by the invention has the advantages that the raw material is cheap and easy to obtain, the operation is simple, the product yield is 85%+ / -5%, and the HPLC purity is larger 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 J(4-N-propionyl[5-methyl-3-(3-N-propionylphenylsulfonamide)-1,2 -oxazol-4-yl] benzenesulfonamide) synthetic method. 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 hype...

Claims

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Application Information

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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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