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Synthesis method for parecoxib sodium impurity

A technology of parecoxib sodium and its synthesis method, which is applied in the field of chemical pharmacy to achieve the effects of easy-to-obtain raw materials, simple operation, and improved quality

Inactive 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 K 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
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Effect test

Embodiment 1

[0021] Embodiment 1: A kind of synthetic method of parecoxib sodium impurity K (N-[[4-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonyl]acetamide)

[0022] Add 20g of dichloromethane and 5g of 5-methyl-3,4-diphenylisoxazole into the reaction bottle, control the reaction temperature below 30°C, add 15g of chlorosulfonic acid dropwise, and raise the temperature to 40-50°C after the addition is complete. Reflux for 3 hours, take a sample every 0.5 hours and monitor it once with TLC (EA:PE=1:3), react until the TLC monitoring 5-methyl-3,4-diphenylisoxazole spot disappears, that is, 5-methyl-3 , 4-diphenylisoxazole reacted completely;

[0023] The reaction solution was cooled to room temperature, added dropwise to 20 g of ice water, and the temperature was controlled below 20 ° C. After the dropwise addition was completed, 15 g of dichloromethane was used to extract the liquid, and the water phase was extracted by adding 10 g of dichloromethane, and the organic phases (intermediate ...

Embodiment 2

[0028] Embodiment 2: A kind of synthetic method of parecoxib sodium impurity K (N-[[4-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonyl]acetamide)

[0029] Add 20g of dichloromethane and 5g of 5-methyl-3,4-diphenylisoxazole into the reaction bottle, control the reaction temperature below 30°C, add 20g of chlorosulfonic acid dropwise, and raise the temperature to 40-50°C after the addition , refluxed for 8 hours, and monitored by TLC (EA:PE=1:3) every 0.5 hours, and reacted until the TLC monitoring 5-methyl-3,4-diphenylisoxazole spot disappeared, that is, 5-methyl- 3,4-Diphenylisoxazole reacts completely;

[0030] The reaction solution was cooled to room temperature, added dropwise to 20 g of ice water, and the temperature was controlled below 20 ° C. After the dropwise addition was completed, 15 g of dichloromethane was used to extract the liquid, and the water phase was extracted by adding 10 g of dichloromethane, and the organic phases (intermediate 1 dichloromethane solution...

Embodiment 3

[0032] Embodiment 3: A kind of synthetic method of parecoxib sodium impurity K (N-[[4-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonyl]acetamide)

[0033] Add 20g of dichloromethane and 5g of 5-methyl-3,4-diphenylisoxazole into the reaction flask, control the reaction temperature below 30°C, add 25g of chlorosulfonic acid dropwise, and raise the temperature to 40-50°C after the addition , refluxing for 6h, sampling every 0.5 hours and monitoring with TLC (EA:PE=1:3), and reacting until the TLC monitoring 5-methyl-3,4-diphenylisoxazole spot disappears, that is, 5-methyl- 3,4-Diphenylisoxazole reacts completely;

[0034]The reaction solution was cooled to room temperature, added dropwise to 20 g of ice water, and the temperature was controlled below 20 ° C. After the dropwise addition was completed, 15 g of dichloromethane was used to extract the liquid, and the water phase was extracted by adding 10 g of dichloromethane, and the organic phases (intermediate 1 (dichloromethane s...

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Abstract

The invention disclose a synthesis method for a parecoxib sodium impurity namely N-[[4-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonyl] acetamide 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 65%+ / -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 K(N-[[4-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonyl] Synthetic method of acetamide). 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 pla...

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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