Synthetic method of imrecoxib

A synthesis method and p-methylphenyl technology, applied in the field of erecoxib synthesis, can solve the problems of many impurities and by-products, unfavorable post-processing and purification, and difficulty in meeting the quality requirements of raw materials, and achieve cost reduction, The effect of less impurities

Active Publication Date: 2018-11-30
SUZHOU FUSHILAI PHARMA CO LTD
View PDF6 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] where R 1 , R 2 Chlorine or bromine, this process route needs to use a strong base as a condensing agent to carry out the cyclization reaction. Since there are many impurities

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
  • Synthetic method of imrecoxib
  • Synthetic method of imrecoxib
  • Synthetic method of imrecoxib

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] A) Synthesis of 3-p-methylphenyl-4-p-methylsulfonylphenylpyrrole-2-carboxylic acid methyl ester:

[0041] (E)-1-p-methylsulfonylphenyl-1-nitro-2-p-tolylethylene (21.0g) was dissolved in isopropanol (300mL), sodium hydroxide (4.0g) was added, stirred and ice-bathed Cool to 5-10°C, add a solution of methyl isocyanoacetate (7.2g) in isopropanol (12mL) dropwise, rise to 30°C and react for 18h until the reaction is complete. After post-treatment, the obtained crude product is recrystallized with ethanol, To obtain methyl 3-p-methylphenyl-4-p-methylsulfonylphenylpyrrole-2-carboxylate, 23.2 g of off-white solid, yield 95%.

[0042] B) Synthesis of 3-p-methylphenyl-4-p-methylsulfonylphenylpyrrole-2-carbaldehyde:

[0043]3-p-methylphenyl-4-p-methylsulfonylphenylpyrrole-2-carboxylic acid methyl ester (23.0g) was dissolved in dichloromethane (350mL), cooled to -78°C, and bis(2-methyl Oxyethoxy) sodium aluminum hydride (13.8g) in n-hexane solution, heat preservation reaction for ...

Embodiment 2

[0049] A) synthesis of 3-p-methylphenyl-4-p-methylsulfonylphenylpyrrole-2-carboxylic acid ethyl ester:

[0050] (E)-1-p-methylsulfonylphenyl-1-nitro-2-p-tolylethylene (12.0g) was dissolved in tetrahydrofuran (180mL), potassium carbonate (9.4g) was added, stirred and cooled to 5 ~10°C, add a solution of ethyl isocyanoacetate (5.6g) in tetrahydrofuran (10mL) dropwise, rise to 35°C and react for 12h until the reaction is complete. Ethylphenyl-4-p-methylsulfonylphenylpyrrole-2-carboxylate, off-white solid 13.5g, yield 93%.

[0051] B) Synthesis of 3-p-methylphenyl-4-p-methylsulfonylphenylpyrrole-2-carbaldehyde:

[0052] 3-p-methylphenyl-4-p-methylsulfonylphenylpyrrole-2-carboxylic acid ethyl ester (13.0g) was dissolved in toluene (180mL), cooled to -78°C, diisobutylaluminum hydride ( 6.3 g) of n-hexane solution, keep it warm for 4 hours until the reaction is complete, add dilute hydrochloric acid dropwise at low temperature to quench the reaction solution, rise to room temperatu...

Embodiment 3

[0058] A) Synthesis of 3-p-methylphenyl-4-p-methylsulfonylphenylpyrrole-2-carboxylic acid methyl ester:

[0059] (E)-1-p-methylsulfonylphenyl-1-nitro-2-p-tolylethylene (5.6g) was dissolved in methanol (100mL), and 1,8-diazabicyclo[5.4.0]deca was added One-carb-7-ene (5.4g), stirred and cooled in an ice bath to 5-10°C, added dropwise a solution of methyl isocyanoacetate (2.6g) in methanol (6mL), raised to 20°C and reacted for 24h until the reaction was complete , after post-treatment, the obtained crude product was recrystallized from ethanol to obtain 3-p-methylphenyl-4-p-methylsulfonylphenylpyrrole-2-carboxylic acid methyl ester, 6.3 g of off-white solid, yield 96%.

[0060] B) Synthesis of 3-p-methylphenyl-4-p-methylsulfonylphenylpyrrole-2-carbaldehyde:

[0061] 3-p-methylphenyl-4-p-methylsulfonylphenylpyrrole-2-carboxylic acid methyl ester (6.2g) was dissolved in chloroform (100mL), cooled to -78°C, diisobutylaluminum hydride ( 3.6 g) of n-hexane solution, heat preservati...

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 discloses a synthetic method of imrecoxib. The synthetic method comprises the following steps: allowing (E)-1-p-methanesulfonylphenyl-1-nitro-2-p-tolylethylene and ethyl isocyanoacetateto undergo a condensation and cyclization reaction in a system containing an alkali reagent and a solvent; allowing the obtained 3-p-methylphenyl-4-p-methylsulfonylphenylpyrrole-2-carboxylate to undergo a reducing reaction at -78 DEG C in a system containing a reducing reagent and a solvent; allowing the obtained 3-p-methylphenyl-4-p-methylsulfonylphenylpyrrole-2-carbaldehyde to undergo an oxidation reaction in a system containing a hydrogen peroxide solution and a solvent; and allowing the obtained 3-p-methylphenyl-4-p-methylsulfonylphenyl-3-pyrrolidin-2-one and 1-halopropane or a hydrocarbonpropyl sulfonate derivative to undergo a substitution reaction in a system containing an alkali reagent and a solvent to obtain the imrecoxib. The synthetic method of the imrecoxib has the beneficialeffects that the reaction steps are simplified and optimized and the process is simple in operation, thereby being helpful to reduce cost; reaction impurities are less and controllable, so greennessand environment-friendliness are embodied; and initial raw materials and the used reagents are easily available.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical chemical synthesis, and in particular relates to a synthesis method of Erecoxib. Background technique [0002] The new COX-2 selective inhibitor Imrecoxib (Imrecoxib) is the first class 1.1 new drug independently developed by Jiangsu Hengrui Company. It is used to treat and relieve the pain symptoms of osteoarthritis and postoperative inflammation. It has been approved by the National FDA listed. Its chemical name is N-n-propyl-3-p-methylphenyl-4-p-methylsulfonylphenyl-3-pyrrolidin-2-one, and its chemical structure is: [0003] [0004] The first-line medication for osteoarthritis will change somewhat in the future, and specific inhibitors of COX-2 (a cyclooxygenase that causes joint pain and inflammation) may replace the current acetaminophen as an osteoarthritis drug. first-line medication. In the changing pattern of first-line drugs for osteoarthritis in the future, Irexix has a go...

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
IPC IPC(8): C07D207/38
CPCC07D207/38
Inventor 莫国宁
Owner SUZHOU FUSHILAI PHARMA CO LTD
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