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

Synthesis method of rivaroxaban

A synthesis method and technology of rivaroxaban, applied in the production of bulk chemicals, organic chemistry and other directions, can solve the problems of unfavorable industrial production, difficult to obtain, high price, etc., to avoid the use of expensive raw materials, improve yield, improve The effect of production efficiency

Inactive Publication Date: 2020-06-09
JIANGSU ZHONGBANG PHARMA +1
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The yield of this route is low, and the raw material (S)-3-amino-1,2-propanediol hydrochloride is rarely sold in the market and is difficult to obtain, and the price is expensive, which is not conducive to industrial 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
  • Synthesis method of rivaroxaban
  • Synthesis method of rivaroxaban
  • Synthesis method of rivaroxaban

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Drop into 4.0g 40% methylamine aqueous solution, 36g ethanol and 7.2g 2-[[(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl) in 100ml four-necked reaction flask Phenyl]-5-oxazolidinyl]methyl]-1H-isoindole-1,3(2H)-dione, stir and heat up to 70°C, keep the temperature for 3 hours, image 3 The main raw material came out at 4.346 minutes, the reaction of the raw material was complete, the system was evaporated to dryness under reduced pressure, 40g of purified water and 2.2g of sodium carbonate were added, stirred to dissolve, and 13.4g of 30% 5-chlorothiophene-2-formyl chloride was added dropwise at 10°C Solution, insulation reaction 1 hour monitoring reaction completes, Figure 4 The main raw material peaked at 2.633 minutes, and the reaction of the raw material was complete. Add 50g of acetone and continue to stir for 0.5 hours, filter to obtain a white solid, rinse with 30g of purified water and 30g of acetone, and dry in vacuum to obtain 6.9g of dry product of rivaroxaban (yield ...

Embodiment 2

[0037] Drop into 4.0g 40% aqueous methylamine solution, 36g methanol and 7.2g 2-[[(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl) in 100ml four-necked reaction flask Phenyl]-5-oxazolidinyl]methyl]-1H-isoindole-1,3(2H)-dione, stir and heat up to 70°C, keep warm for 3 hours, evaporate the system to dryness under reduced pressure, add 40g Purified water and 2.2g of sodium carbonate were stirred and dissolved, and 13.4g of 30% 5-chlorothiophene-2-formyl chloride toluene solution was added dropwise at 10°C, and kept for 1 hour to monitor the completion of the reaction, and 50g of acetone was added to continue stirring for 0.5 hours, and filtered to obtain white The solid was rinsed with 30 g of purified water and 30 g of acetone, respectively, and dried under vacuum to obtain 6.7 g of dry product of rivaroxaban (90.0% yield, 99.88% purity);

Embodiment 3

[0039]Drop into 4.0g 40% methylamine aqueous solution, 36g ethanol and 7.2g 2-[[(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl) in 100ml four-necked reaction flask Phenyl]-5-oxazolidinyl]methyl]-1H-isoindole-1,3(2H)-dione, stir and heat up to 60°C, keep warm for 3 hours, evaporate the system to dryness under reduced pressure, add 40g Purified water and 2.2g of sodium carbonate were stirred and dissolved, and 13.4g of 30% 5-chlorothiophene-2-formyl chloride toluene solution was added dropwise at 10°C, and kept for 1 hour to monitor the completion of the reaction, and 50g of acetone was added to continue stirring for 0.5 hours, and filtered to obtain white The solid was rinsed with 30 g of purified water and 30 g of acetone, respectively, and dried under vacuum to obtain 6.8 g of dry product of rivaroxaban (91.3% yield, 99.83% purity);

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 rivaroxaban. According to the method, rivaroxaban is prepared by adopting a one-pot method; 2-[[(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-5-oxazolidinyl]methyl]-1H-isoindol-1,3(2H)-one in an alcohol solvent is subjected to an ammonolysis reaction in the presence of an alkali to remove a protective group, then to evaporation to remove the alcohol solvent, and finally to condensation with 5-chlorothiophene-2-formyl chloride under the action of an acid-binding agent, wherein the reaction alcohol solvent is alcohol with a carbon number of 4 or below, the alkali is an organic alkali or inorganic alkali, a condensation reaction solvent is water, and the acid-binding agent is potassium carbonate or sodium carbonate. The method has the advantages ofmild reaction conditions, simple post-treatment, conservation of a large amount of manpower and material resources, and applicability to large-scale industrial production.

Description

Technical field: [0001] The invention relates to a synthesis method of rivaroxaban, in particular to a method for preparing rivaroxaban by a one-pot method, and belongs to the technical field of chemical drug synthesis. Background technique: [0002] Rivaroxaban, English name Rivaroxaban, domestic product name is Xarelto, CAS number: 366789-02-8, molecular formula: C 19 h 18 ClN 3 o 5 S, its structural formula is as follows (formula 1): [0003] [0004] Rivaroxaban is a new oral anticoagulant drug jointly developed by Bayer and Johnson & Johnson. It was approved for marketing in Canada and the European Union on September 15 and October 1, 2008, respectively. Now approved for marketing in 29 countries including China, it is used to prevent the formation of venous thromboembolism and pulmonary embolism after hip and knee replacement surgery in adult patients. On June 19, 2009, Rivaroxaban was approved by the State Food and Drug Administration and launched in China...

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): C07D413/14
CPCC07D413/14Y02P20/55
Inventor 薛谊吴小刚刘力萍唐景玉高倩秦春梅
Owner JIANGSU ZHONGBANG PHARMA
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