Preparation method of anhydrous and non-solvation A crystallization parecoxib sodium

A technology of parecoxib sodium and parecoxib, which is applied in the field of preparation of anhydrous, non-solvated A crystal form parecoxib sodium, and can solve high equipment requirements, high safety requirements, and long reaction time And other issues

CN104910091AInactive Publication Date: 2015-09-16北京华睿鼎信科技有限公司
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Publication Date
2015-09-16
Estimated Expiration
Not applicable · inactive patent

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Abstract

The invention relates to a preparation method of anhydrous and non-solvation A crystallization parecoxib sodium. The method comprises the following steps: 1,2-phenylacetophenone and pyrrolidine are condensed to generate 1-(1,2-diphenylvinyl)pyrrolidine, then acetylation is carried out, and 4,5-dihydro-5-methyl-3,4-dibenzyl-5-isoxzzole alcohol are subjected to cyclization under sodium acetate and hydroxylamine hydrochloride. The compound is directly reacted to chlorosulfonic acid, dehydration and chlorine sulfonation reaction are carried out, and then valdecoxib can be obtained through ammonification, valdecoxib is refined, then is subjected to acetylation to obtain parecoxib, and salt forming is performed to obtain the target compound parecoxib sodium.
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Description

technical field

[0001] The invention relates to the technical field of chemical synthesis, in particular to a method for preparing anhydrous, non-solvated A crystal form parecoxib sodium. Background technique

[0002] Parecoxib sodium has the following structural formula:

[0003]

[0004] It is the world's first specific cyclooxygenase-2 (COX-2) inhibitor that can be administered intravenously and intramuscularly. It is a water-soluble prodrug of valdecoxib and belongs to the coxib in anti-arthritic drugs Clinically, it is mainly used for the short-term treatment of postoperative pain, and can also be used for the treatment of moderate or severe postoperative acute pain. Compared with opioids, selective COX-2 inhibitors can effectively inhibit the expression of peripheral and central COX-2, reduce the synthesis of peripheral and central prostaglandins, inhibit hyperalgesia, increase pain threshold, and have dual analgesic advantages. The analgesic efficacy of parecoxib...

Examples

Embodiment 1

[0068] (1) Preparation of 1-(1,2-diphenylvinyl)pyrrolidine (DPVP)

[0069] Add 304.0g of 1,2-diphenylethanone, 335.2g of pyrrolidine, 9.3g of glacial acetic acid, and 808.6g of cyclohexane to a 3L three-necked round-bottomed flask equipped with a Dean / Stark water separator and a reflux condenser, and stir Control the temperature of the feed liquid to rise to 80±5°C, and stir the reaction at this temperature, and track and detect the reaction process according to the water separation of the Dean / Stark water separator. After the reaction was completed, the reaction solution was cooled to 30±5°C, concentrated under reduced pressure at 70±5°C until no organic solvent was distilled off, and 430.6 g of a brown viscous liquid product was obtained.

[0070] (2) Preparation of 4,5-dihydro-5-methyl-3,4-diphenyl-5-isoxazolol (MPHI)

[0071]The viscous liquid obtained in the above steps was placed in a round bottom flask, and 391.4 g of acetonitrile was added, and stirred to make it diss...