Preparation methods of parecoxib sodium and intermediate thereof

A technique for parecoxib sodium and intermediates, which is applied in the field of preparation of parecoxib sodium and its intermediates, can solve the problems of unsuitability for industrial production, low reaction yield, high production cost, etc., and achieve low cost and high purity High, responsive and easy post-processing effects

A technique for parecoxib sodium and intermediates, which is applied in the field of preparation of parecoxib sodium and its intermediates, can solve the problems of unsuitability for industrial production, low reaction yield, high production cost, etc., and achieve low cost and high purity High, responsive and easy post-processing effects

CN106674142AInactive Publication Date: 2017-05-17SHANGHAI BOCIMED PHARMA CO LTD
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  • Preparation methods of parecoxib sodium and intermediate thereof
  • Preparation methods of parecoxib sodium and intermediate thereof
  • Preparation methods of parecoxib sodium and intermediate thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Embodiment 1: the preparation method of parecoxib sodium intermediate I

[0039]

[0040] The raw material valdecoxib III (5.0 g) was added to propionic anhydride (18.6 g), and stirred to dissolve. Add sulfamic acid (0.15g), heat up to 50-60°C, and react for about 3 hours. TLC monitors that the reaction is complete, cools down to about 0°C, and keeps stirring for about 1 hour. Filter, rinse the filter cake with methyl tert-butyl ether (10ml) and place it in a vacuum oven at -0.08MPa~-0.1MPa, and dry it in vacuum at 50°C for 8-12 hours to obtain 4.77g of the intermediate of parecoxib sodium 1, yield 81%. The HPLC purity is 99.91%, the maximum impurity is 0.06%, and the raw material valdecoxib III is <0.02%.

Embodiment 2

[0041] Embodiment 2: the preparation method of parecoxib sodium intermediate I

[0042] The raw material valdecoxib III (10.0 kg) was added to propionic anhydride (37.2 kg), stirred and dissolved. Add sulfamic acid (0.31kg), heat up to 50-60°C, and react for about 4 hours. TLC monitors that the reaction is complete, cools down to about 0°C, and keeps stirring for about 1 hour. After centrifugation, the filter cake was rinsed with methyl tert-butyl ether (20L) and placed in a vacuum oven at -0.08MPa~-0.1MPa, and dried at 50°C for 8-12 hours to obtain the parecoxib sodium intermediate (I) 9.31kg, yield 79.2%. The HPLC purity is 99.92%, the maximum single impurity is 0.05%, and the raw material valdecoxib III is <0.02%.

Embodiment 3

[0043] Embodiment 3: the preparation method of parecoxib sodium intermediate I

[0044] The raw material valdecoxib III (5.0 g) was added to propionic anhydride (18.6 g), and stirred to dissolve. Add methanesulfonic acid (0.15 g), heat up to 50-60° C., and react for about 3 hours. TLC monitors that the reaction is complete, cools down to about 0°C, and keeps stirring for about 1 hour. Filtrate, rinse the filter cake with methyl tert-butyl ether (10ml) and place it in a vacuum oven at -0.08MPa~-0.1MPa, and dry it in vacuum at 50°C for 8-12 hours to obtain 4.80g of parecoxib sodium intermediate 1, yield 81.5%. The HPLC purity is 99.90%, the maximum impurity is 0.07%, and the raw material valdecoxib III is <0.02%.

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Abstract

The invention discloses preparation methods of parecoxib sodium and intermediate thereof. The invention provides a preparation method of a parecoxib sodium intermediate I. The preparation method of the parecoxib sodium intermediate I comprises the following step: in the presence of a catalyst, performing condensation reaction on valdecoxib III and propionic anhydride to obtain the parecoxib sodium intermediate I, wherein the catalyst is one or more of benzenesulfonic acid, p-toluenesulfonic acid, methanesulfonic acid and sulfamic acid. The preparation method is simple in reaction and post-treating operation, high in yield and low in cost; the purity of the prepared intermediate product is high and can reach 99.80% or above, and the content of specific impurity valdecoxib reaches 0.02% or below and can meet the standard of an original researching manufacturer; therefore, the preparation method is suitable for industrial production. The purity of parecoxib sodium prepared from the parecoxib sodium intermediate I prepared by the preparation method provided by the invention can reach 99.80% or above and the content of the specific impurity valdecoxib reaches 0.01% or below and is higher than the standard of the original researching manufacturer.

Description

technical field [0001] The invention relates to a preparation method of parecoxib sodium and an intermediate thereof. Background technique [0002] Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat inflammation and ailments, for example in arthritis and headaches. Such drugs are effective, but their long-term use is limited by gastrointestinal side effects including dyspepsia and abdominal pain and, in severe cases, gastric or duodenal perforation and / or bleeding, by combining the therapeutic efficacy of traditional NSAIDs Along with a vastly improved gastrointestinal safety profile, the development of selective COX-2 inhibitory drugs has revolutionized the treatment of inflammation and pain. Cyclooxygenase (COX) inhibition is believed to be at least the primary mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) exert their characteristic anti-inflammatory, antipyretic and analgesic effects through inhibition of prostaglandin synthesis. ...

Claims

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Application Information

Patent Timeline
17 May 2017
Publication
CN106674142A
IPC
C07D261/08
CPC
C07D261/08
Inventors
应述欢; 皮红军