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A method for preparing parecoxib for treating postoperative pain

A technology of parecoxib and methyl, which is applied in the field of drug synthesis, can solve the problems of high equipment requirements, low overall yield, environmental pollution, etc., and achieve the effect of simple reaction treatment, simple reaction steps, and improved reaction yield

Active Publication Date: 2018-11-06
TAIZHOU BAOCHENG TECH SERVICES CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The above method has long steps and low overall yield. The reason is mainly because of the cyclization step for the preparation of intermediate 5-methyl-3,4-diphenylisoxazole, and acetyl oxygen will also participate in the reaction of hydroxylamine to generate By-products; in addition, the elimination step uses trifluoroacetic acid system for dehydration, which requires high equipment, and fluoride will also cause environmental pollution

Method used

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  • A method for preparing parecoxib for treating postoperative pain
  • A method for preparing parecoxib for treating postoperative pain
  • A method for preparing parecoxib for treating postoperative pain

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Preparation of 5-methyl-3,4-diphenylisoxazole

[0028] 29.1 g (100 mmol) of 3,4-diphenyl-4-(1-pyrrolidinyl)-3-buten-2-one and 30.8 g (400 mmol) of ammonium acetate were added to a flask containing 30 ml of acetic acid, Contact reaction at 65°C for 1 hour. After the reaction, dilute with dichloromethane, adjust the pH to 7 with saturated sodium bicarbonate, concentrate the organic phase, wash with water, recrystallize with ethanol, and dry to obtain 5-methyl-3,4-diphenyl Isoxazole 20.6g, yield 87.5%, purity 99.67%.

Embodiment 2

[0030] Preparation of 5-methyl-3,4-diphenylisoxazole

[0031] 29.1 g (100 mmol) of 3,4-diphenyl-4-(1-pyrrolidinyl)-3-buten-2-one and 38.5 g (500 mmol) of ammonium acetate were added to a flask containing 31 ml of acetic acid, Contact reaction at 70°C for 1 hour. After the reaction, dilute with dichloromethane, adjust the pH to 6 with saturated sodium bicarbonate, concentrate the organic phase, wash with water, recrystallize with ethanol, and dry to obtain 5-methyl-3,4-diphenyl 20.5 g of isoxazole, the yield is 87.4%, and the purity is 99.71%.

Embodiment 3

[0033] Preparation of 5-methyl-3,4-diphenylisoxazole

[0034] 29.1 g (100 mmol) of 3,4-diphenyl-4-(1-pyrrolidinyl)-3-buten-2-one and 23.1 g (300 mmol) of ammonium acetate were added to a flask containing 90 ml of acetic acid, Contact reaction at 80°C for 1.5 hours. After the reaction, dilute with dichloromethane, adjust the pH to 6 with saturated sodium bicarbonate, concentrate the organic phase, wash with water, recrystallize with ethanol, and dry to obtain 5-methyl-3,4-diphenyl Isoxazole 20.3g, yield 86.3%, purity 99.60%.

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Abstract

The invention discloses a method for preparing parecoxib for treating postoperative pain. The method comprises the following steps: 1) conducting a contact reaction between 3,4-diphenyl-4-(1-pyrrolidyl)-3-butene-2-one and ammonium acetate in acetic acid; after the reaction, diluting dichloromethane; regulating the pH value to 6-7 with saturated sodium bicarbonate; concentrating the organic phase and washing; recrystallizing with ethanol; and drying to obtain 5-methyl-3,4-diphenyl isoxazole; 2) stirring the obtained 5-methyl-3,4-diphenyl isoxazole and chlorosulfonic acid for reacting; adding anion exchange resin, and dropwise adding saturated ammonium chloride and dichloromethane for extraction; 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 method for preparing parecoxib, disclosed by the invention, has the advantages of simple steps, mild conditions and high yield.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and in particular relates to a method for preparing parecoxib for treating postoperative pain. 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 o...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D261/08A61P29/00
CPCC07D261/08
Inventor 王晓岳
Owner TAIZHOU BAOCHENG TECH SERVICES CO LTD
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