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

Inactive Publication Date: 2015-09-16
北京华睿鼎信科技有限公司
View PDF4 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Its main disadvantages are: butyllithium has high chemical reactivity and high safety requirements for the reaction, which is not conducive to industrial production, and fluoride is more serious to the environment, which increases the difficulty of three wastes treatment
The main disadvantage of this method is: the reaction requires the use of more expensive reagents, such as chloroacetylation requires the use of expensive 2,6-lutidine as an acidic agent, and the reaction time is relatively long, requiring 24 hours, the reaction system It is acidic, requires high equipment, and increases production costs. At the same time, this process uses trifluoroacetic acid as a dehydration medium, which will also be affected by fluoride
The raw material of this method is more expensive, and the source of benzonitrile N oxide is limited, so this method is not suitable for industrialized production

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method of anhydrous and non-solvation A crystallization parecoxib sodium
  • Preparation method of anhydrous and non-solvation A crystallization parecoxib sodium
  • Preparation method of anhydrous and non-solvation A crystallization parecoxib sodium

Examples

Experimental program
Comparison scheme
Effect test

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...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

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.

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...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C07D261/08
Inventor 安明张旭
Owner 北京华睿鼎信科技有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap