A kind of preparation method of cyclooxygenase-2 inhibitor parecoxib intermediate

A technology of parecoxib and cyclooxygenase, which is applied in the field of drug synthesis, can solve the problems of fluoride environmental pollution, complex reaction steps, and high equipment requirements, and achieve the effects of increased reaction yield, mild conditions, and simple reaction steps

A technology of parecoxib and cyclooxygenase, which is applied in the field of drug synthesis, can solve the problems of fluoride environmental pollution, complex reaction steps, and high equipment requirements, and achieve the effects of increased reaction yield, mild conditions, and simple reaction steps

CN105968065BInactive Publication Date: 2018-06-26摹斜燕 +1
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  • A kind of preparation method of cyclooxygenase-2 inhibitor parecoxib intermediate
  • A kind of preparation method of cyclooxygenase-2 inhibitor parecoxib intermediate
  • A kind of preparation method of cyclooxygenase-2 inhibitor parecoxib intermediate

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Embodiment 1

[0021] A method for preparing a parecoxib intermediate, the method comprising: 29.1 g (100 mmol) of 1-phenyl-2-(4-sulfonic acid phenyl)-2-acetyl ethyl ketone, 30.8 g of ammonium acetate (400mmol), iodobenzene diacetate 19.3g (60mmol), potassium iodide 6.6g (40mmol) join in the flask that 150ml dichloromethane is housed, 75 ℃ carry out contact reaction 1 hour, after reaction finishes, organic phase concentration, washing, Wash with saturated brine, dry over anhydrous sodium sulfate, then recrystallize from ethanol, and dry to obtain 27.5 g of the parecoxib intermediate 5-methyl-3,4-diphenylisoxazole with a yield of 87.3% and a purity of 99.60 %.

Embodiment 2

[0023] A method for preparing parecoxib intermediate, the method comprising: 29.1g (100mmol) of 1-phenyl-2-(4-sulfonic acid phenyl)-2-acetyl ethyl ketone, 38.5g of ammonium acetate (500mmol), iodobenzene diacetate 22.5g (70mmol), potassium iodide 9.9g (60mmol) join in the flask that 150ml dichloromethane is housed, 80 ℃ carry out contact reaction 1 hour, after reaction finishes, organic phase is concentrated, washed, Washed with saturated brine, dried over anhydrous sodium sulfate, recrystallized from ethanol, and dried to obtain 27.4 g of the parecoxib intermediate 5-methyl-3,4-diphenylisoxazole with a yield of 86.8% and a purity of 99.71 %.

Embodiment 3

[0025] A method for preparing parecoxib intermediate, the method comprising: 29.1g (100mmol) of 1-phenyl-2-(4-sulfonic acid phenyl)-2-acetyl ethyl ketone, 38.5g of ammonium acetate (500mmol), iodobenzene diacetate 19.3g (60mmol), potassium iodide 6.6g (40mmol) join in the flask that 150ml dichloromethane is housed, 85 ℃ carry out contact reaction 0.5 hour, after reaction finishes, organic phase is concentrated, washed, Washed with saturated brine, dried over anhydrous sodium sulfate, then recrystallized from ethanol, and dried to obtain 26.5 g of the parecoxib intermediate 5-methyl-3,4-diphenylisoxazole with a yield of 84.5% and a purity of 99.33 %.

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Abstract

The invention discloses a preparation method of a cyclooxygenase-2 inhibitor parecoxib intermediate. The preparation method comprises the following steps: in the presence of iodobenzene diacetate and potassium iodide, carrying out contact reaction on 1-phenyl-2-(4-sulfophenyl)-2-acetylethylketone and ammonium acetate; and after the reaction finishes, concentrating the organic phase, washing with water, recrystallizing with ethanol, and drying to obtain the 5-methyl-3-phenyl-4-(4-sulfophenyl)isoxazole. The method for preparing the parecoxib intermediate 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 preparation method of a cyclooxygenase-2 inhibitor parecoxib intermediate. 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 dehyd...

Claims

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Application Information

Patent Timeline
26 Jun 2018
Publication
CN105968065B
IPC
C07D261/08
CPC
C07D261/08
Inventors
摹斜燕; æ›ČćźȘ揌