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

New method for synthesizing rivaroxaban intermediate 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidine-3-yl]phenyl}morpholine-3-ketone

A technology of aminomethyl and rivaroxaban, which is applied in the direction of organic chemistry, can solve the problems of high energy consumption, increased reaction steps and costs, and long reaction time, and achieves mild reaction conditions, low production cost, and simple operation. Effect

Active Publication Date: 2012-12-19
SHANGHAI SYNCORES TECH INC
View PDF3 Cites 12 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] 1) The price of the raw material 2-[(2S)-2-oxiranyl-methyl]-1-H-isoindole-1,3(2H)-dione is relatively high, and rivaroxabanoxazole The nitrogen atom on the alkanone ring is protected by phthalimide, and methylamine needs to be used to remove the protecting group, which increases the reaction steps and cost
[0011] 2) Heating is required during the reaction, the reaction time is too long, the energy consumption is large, the cost is high, and it is not suitable for 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
  • New method for synthesizing rivaroxaban intermediate 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidine-3-yl]phenyl}morpholine-3-ketone
  • New method for synthesizing rivaroxaban intermediate 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidine-3-yl]phenyl}morpholine-3-ketone
  • New method for synthesizing rivaroxaban intermediate 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidine-3-yl]phenyl}morpholine-3-ketone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Preparation of compound 3

[0027] Add 8.35g of compound 1 and 5.0g of compound 2 into 30ml of tetrahydrofuran, cool down to 10°C in an ice bath, slowly add 6.4g of lithium tert-butoxide, react the mixture at 20~30°C for 24 hours, add 100ml of water and 100ml of dichloromethane , after stirring, let it stand for liquid separation, concentrate the dichloromethane layer to dryness, heat to dissolve with 20ml of toluene, stir and cool down to 5~10°C to precipitate a solid, and suction filter to obtain 7.0 g of an off-white solid, with a yield of 90%.

Embodiment 2

[0029] Preparation of compound 3

[0030] Add 25.0 g of compound 1 and 15.0 g of compound 2 into a mixed solvent of 30 ml of N,N-dimethylformamide and 50 ml of tetrahydrofuran, cool down to 10°C in an ice bath, and slowly add 20 g of lithium tert-butoxide, and the mixture is at 20 React at ~30°C for 24 hours, add 300ml of water and 300ml of dichloromethane, stir and let stand to separate liquids, concentrate the dichloromethane layer to dryness, heat to dissolve with 40ml of toluene, stir and cool down to 5~10°C to precipitate solids, and filter with suction to obtain Off-white solid 22.7 g, yield 97%.

[0031]

Embodiment 3

[0033] Preparation of compound 3

[0034] Add 1.7 g of compound 1 and 1.0 g of compound 2 into a mixed solvent of 2 ml of N,N-dimethylformamide and 4 ml of tetrahydrofuran, cool down to 10°C in an ice bath, and slowly add 0.7 g of lithium methoxide. React at ℃ for 24 hours, add 20ml of water and 20ml of dichloromethane, stir and then let stand to separate the liquids, concentrate the dichloromethane layer to dryness, heat and dissolve with 2ml of toluene, cool down to 5~10℃ to precipitate a solid, and suction filter to obtain an off-white solid 0.97 g, 62% yield.

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 new method for synthesizing rivaroxaban intermediate 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidine-3-yl]phenyl}morpholine-3-ketone. The method comprises the following steps: reacting a compound 1 and a compound 2 in an inert solvent in the presence of lithium to get a compound 3; and carrying out an ester group removing reaction under the effect of hydrochloric acid or hydrogen chloride to get a compound 4, that is, 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidine-3-yl]phenyl}morpholine-3-ketone. The new method provided by the invention has advantages of mild reaction condition, simple operation, easy purification and low production cost, and is environmentally friendly and suitable for industrial production.

Description

technical field [0001] The present invention relates to the synthesis of pharmaceutical intermediates, more specifically to a synthetic anticoagulant drug rivaroxaban intermediate, namely 4-{4-[(5S)-5-(aminomethyl)-2-oxo -1,3-Oxazolidin-3-yl]phenyl}morpholin-3-one new method. Background technique [0002] Rivaroxaban (Rivaroxaban), the chemical name is 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1 , 3-oxazolidin-5-yl}methyl-2-thiophenecarboxamide, its structural formula (I) is as follows: [0003] [0004] Rivaroxaban, a new type of highly selective anticoagulant drug developed by Bayer in Germany, is called Rivaroxaban in English. Rivaroxaban was approved by the European Commission in September 2008, and its trade name is Xarelto. Rivaroxaban competitively inhibits free and bound factor Xa and prothrombin activity, prolonging prothrombin time (PT) and activated partial thromboplastin time (APTT) in a dose-dependent manner for the prevention of hip and kne...

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): C07D413/10
CPCC07D413/10
Inventor 资春鹏黄鲁宁张席妮
Owner SHANGHAI SYNCORES TECH INC
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