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Method for preparing cyclooxygenase-2 inhibitor parecoxib

A technology of cyclooxygenase and valdecoxib, which is applied in the direction of organic chemistry, can solve the problems of waste discharge operator safety impact, compound corrosiveness, and difficult reaction treatment, so as to reduce the reaction time, increase the reaction yield, The effect of simple reaction steps

Active Publication Date: 2016-10-12
鄂东医疗集团市中心医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] CN105418528A discloses a preparation method of parecoxib sodium, which innovatively adopts a dipolar cycloaddition reaction to synthesize an isoxazole ring with benzaldoxime and 1-phenyl-1-propyne in the presence of a catalyst, The yield has also reached a relatively high level, but the catalyst chlorosuccinimide used in large quantities in this method is even up to 3 times the amount, which makes the reaction treatment more difficult, and the compound is corrosive, requires high equipment, and a large amount of Emission of waste and impact on operator safety

Method used

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  • Method for preparing cyclooxygenase-2 inhibitor parecoxib
  • Method for preparing cyclooxygenase-2 inhibitor parecoxib
  • Method for preparing cyclooxygenase-2 inhibitor parecoxib

Examples

Experimental program
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Effect test

Embodiment 1

[0025] Preparation of 5-methyl-3-phenyl-4-(4-sulfophenyl)isoxazole

[0026] Mix 12.1g (100mmol) of benzaldoxime with 23.5g (120mmol) of 1-(4-sulfophenyl) propyne, 1.9g (3mmol) of tris(2-phenylpyridine) iridium(III), triethyl Add 8.1g (80mmol) of amine and 1g (25mmol) of magnesium oxide into a flask filled with 30ml THF, and carry out the light reaction at 25°C for 30min. The light is emitted by a blue light-emitting diode with a wavelength of 455nm. The reaction solution was concentrated, washed with water, recrystallized from ethanol, and dried to obtain 31.1 g of 5-methyl-3-phenyl-4-(4-sulfophenyl)isoxazole with a yield of 98.7% and a purity of 99.69%.

Embodiment 2

[0028] Preparation of 5-methyl-3-phenyl-4-(4-sulfophenyl)isoxazole

[0029] Mix 12.1g (100mmol) of benzaldoxime with 21.6g (110mmol) of 1-(4-sulfophenyl) propyne, 3.3g (5mmol) of tris(2-phenylpyridine) iridium(III), triethyl Add 8.1g (80mmol) of amine and 1.2g (30mmol) of magnesium oxide into a flask filled with 30ml THF, and carry out the light reaction at 25°C for 30min. The light is emitted by a blue light-emitting diode with a wavelength of 455nm. The reaction solution was concentrated, washed with water, recrystallized from ethanol, and dried to obtain 31.2 g of 5-methyl-3-phenyl-4-(4-sulfophenyl)isoxazole with a yield of 98.9% and a purity of 99.50%.

Embodiment 3

[0031] Preparation of 5-methyl-3-phenyl-4-(4-sulfophenyl)isoxazole

[0032] Mix 12.1g (100mmol) of benzaldoxime with 25.5g (130mmol) of 1-(4-sulfophenyl) propyne, 2.6g (4mmol) of tris(2-phenylpyridine) iridium(III), triethyl Add 7.1g (70mmol) of amine and 1g (25mmol) of magnesium oxide into a flask containing 30ml of THF, and carry out the light reaction at 30°C for 40min. The light is emitted by a blue light-emitting diode with a wavelength of 460nm. The reaction solution was concentrated, washed with water, recrystallized from ethanol, and dried to obtain 30.7 g of 5-methyl-3-phenyl-4-(4-sulfophenyl)isoxazole with a yield of 97.4% and a purity of 99.42%.

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Abstract

The invention discloses a method for preparing a cyclooxygenase-2 inhibitor parecoxib. The method comprises the following steps: 1) enabling benzaldoxime and 1-(4-sulfonyl phenyl)propyne to react in an illumination condition in the presence of tri(2-phenylpyridine)iridium (III), triethylamine and magnesium oxide to obtain 5-methyl-3-phenyl-4-(4-sulfonyl phenyl)isoxazole; 2) conducting a contact reaction between 5-methyl-3-phenyl-4-(4-sulfonyl phenyl)isoxazole obtained in the step 1) and thionyl chloride; after the reaction, extracting dichloromethane; directly adding the dichloromethane phase into ammonia water; separating organic phase; washing and concentrating; and recrystallizing with ethanol to obtain valdecoxib; and 3) enabling the valdecoxib obtained in the step 2) to react with propionic anhydride in the presence of triethylamine to obtain parecoxib. The parecoxib preparation method disclosed by the invention has the advantages of simple steps, high yield and simple aftertreatment.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and in particular relates to a method for preparing cyclooxygenase-2 inhibitor parecoxib. Background technique [0002] Parecoxib Sodium (Parecoxib Sodium) is a specific cyclooxygenase-2 inhibitor that can be given intravenously and intramuscularly. . The chemical name of parecoxib sodium is N-[[4-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonyl]propionamide sodium salt, and the specific structure is as follows: [0003] [0004] At present, there are many studies on the synthesis method of parecoxib (sodium), but basically all of them use 5-methyl-3,4-diphenylisoxazole as the key intermediate to prepare parecoxib. For example, WO2005123701A1 discloses a preparation method of parecoxib, which uses diacetophenone as a starting material, first reacts with tetrahydropyrrole, and then undergoes acetylation, ring-closure reaction with hydroxylamine hydrochloride, elimination and dehydration to obtain...

Claims

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Application Information

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IPC IPC(8): C07D261/08
CPCC07D261/08
Inventor 王晓岳
Owner 鄂东医疗集团市中心医院
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