Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Montelukast sodium intermediate, preparation method thereof and preparation method of montelukast sodium intermediate

A technology for montelukast sodium and intermediates, applied in the field of medicinal chemistry, can solve the problems affecting the large-scale production of montelukast sodium intermediates, long synthetic routes, high production costs, etc., and achieve low production costs and simple post-processing , the effect of high yield

Pending Publication Date: 2022-06-07
JIANGSU ALPHA PHARM CO LTD
View PDF2 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The technical problem to be solved by the present invention is the influence of long synthetic route, high production cost and low yield in the technical scheme of preparing 1-mercaptomethylcyclopropylacetic acid by 1,1-cyclopropyldimethanol at present. Problems in large-scale production of Montelukast sodium intermediate

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
  • Montelukast sodium intermediate, preparation method thereof and preparation method of montelukast sodium intermediate
  • Montelukast sodium intermediate, preparation method thereof and preparation method of montelukast sodium intermediate
  • Montelukast sodium intermediate, preparation method thereof and preparation method of montelukast sodium intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] The preparation of embodiment 1 compound V

[0040]

[0041] Compound VI (30.6 g, 0.3 mol) was dissolved in 300 ml of dichloromethane. To this mixture was added SOCl 2 (166.6 g, 1.4 mol). The obtained mixture was heated to 40-80° C. for 8-12 hours, and then the obtained mixture was evaporated to dryness to obtain 38.04 g of compound V with a yield of 91.2% and a purity of 99.2%.

Embodiment 2

[0042] The preparation of embodiment 2 compound IV

[0043]

[0044] Under nitrogen protection, compound V (27.8 g, 0.2 mol) was added to 100 ml of N,N-dimethylformamide, followed by sodium cyanide (14.7 g, 0.3 mol). The reaction mixture was heated to 80°C and stirred for 2 hours. After the reaction was completed, the resulting mixture was cooled to 20-25°C. 100 mL of water and 100 mL of toluene were added to the reaction mixture, the layers were separated, the aqueous layer was back-extracted with 100 mL of toluene, the organic layers were combined, and concentrated to obtain 24.57 g of compound I with a yield of 94.8% and a purity of 99.5%.

Embodiment 3

[0046]

[0047] (1) Preparation of compound III

[0048] Compound IV (25.9 g, 0.2 mol), thiourea (16 g, 0.21 mol) and 100 ml of acetone were added to the reaction flask, and the mixture was stirred and heated to reflux for 10 hours. The reaction mixture was then cooled to below 0°C, stirred for at least 1 hour, and filtered to obtain a filter cake, which was washed with 2 x 50 ml of acetone. Then, 100 ml of acetone was added to the container containing the filter cake and slurried for 5 hours. The mixture was filtered and washed with 2×25 ml of acetone, and after vacuum drying, 40.44 g of compound III was obtained in a yield of 98.3% and a purity of 99.5%.

[0049] (2) Preparation of Compound I

[0050] Under nitrogen protection, compound III (20.6 g, 0.1 mol) and 60 ml of 30% sodium hydroxide solution (containing 0.6 mol of sodium hydroxide) were added to the reaction flask. The mixture was stirred and heated to reflux for about 14 hours. After cooling to room temperat...

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 the field of medical chemistry, in particular to a montelukast side chain intermediate, a preparation method thereof and a method for applying the intermediate. The invention discloses a novel montelukast side chain intermediate, which is characterized in that 1, 1-cyclopropane dimethyl carbinol is used as a raw material to obtain a novel intermediate compound through chlorination, then cyano substitution, sulfuration reaction and alkaline hydrolysis are performed to obtain a target compound 1-mercaptomethyl cyclopropyl acetic acid, ring closing and ring opening are not required in the process, the whole preparation process is simple in process, the yield is high, and the method is suitable for industrial production. According to experiments, the synthesis route is high in yield, the final product is high in purity, post-treatment is simple, the utilization rate of the raw material 1, 1-cyclopropane dimethyl carbinol can be greatly increased, and compared with a synthesis technology in the prior art, the production cost is low, and the requirements of industrial large-scale production are met.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a side chain intermediate of montelukast sodium, a preparation method thereof and a method for applying the intermediate. Background technique [0002] Montelukast sodium, an anti-asthma, anti-inflammatory and anti-allergic drug, is used for the prevention and long-term treatment of asthma, including the prevention of daytime and nighttime asthma symptoms, the treatment of aspirin-sensitive asthma patients, and the prevention of exercise-induced asthma of bronchoconstriction. Its chemical name is 1-[[[(1R)-1-[3-[(1E)-2-(7-chloro-2-quinoline)vinyl]phenyl]-3-[2-(1- Hydroxy-1-methylethyl) phenyl] propyl] thio] methyl] sodium cyclopropane acetate, the structural formula is as follows: [0003] [0004] The side chain moiety 1-mercaptomethylcyclopropylacetic acid or its derivatives is the key intermediate in the synthesis of montelukast sodium. 1-Mercaptomethylcyclopropylaceti...

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): C07C22/00C07C17/16C07C319/02C07C323/55C07C335/32C07C327/32
CPCC07C22/00C07C17/16C07C319/02C07C335/32C07C327/32C07C2601/02C07C323/55Y02P20/55
Inventor 石利平尹强徐春涛邱磊宋继国万新强孙伟振朱萍
Owner JIANGSU ALPHA PHARM CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com