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

Preparation method and application of rivaroxaban intermediate (S)-N-epoxy propyl phthalimide

A technology of glycidyl phthalimide and potassium phthalimide, which is applied in the direction of organic chemistry, etc., can solve the problems of low yield and severe reaction conditions, and achieve simple reaction, The effect of high yield and mild conditions

Inactive Publication Date: 2015-07-29
ZHEJIANG TIANSHUN BIOTECH
View PDF3 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

(S)-N-Glycidyl phthalimide is an important intermediate of rivaroxaban, but (S)-N-Glycidyl phthalimide existing Several synthetic routes have problems such as low yield or severe reaction conditions

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Preparation of Phthalimide Potassium Salt

[0021] In a 2500mL round bottom flask containing 100g (0.68mol) of phthalimide, add 800mL of absolute ethanol, and add 80g·L dropwise under stirring. -1 KOH methanol solution 480mL (after 1h addition, KOH 0.69mol). Stirring was continued at room temperature for 3 h, filtered, and the resulting white solid was rinsed with absolute ethanol and dried, with a mass of 124 g.

Embodiment 2

[0023] Add 3.1g of phthalimide potassium salt into 15mL (R)-epichlorohydrin, and heat the reaction in an oil bath at 130°C to obtain 2S-(oxane-2-methyl)isoindoline-1 , 3-diketone, the reaction time is 15h. After the reaction was completed, it was distilled under reduced pressure, dried, and recrystallized with petroleum ether.

Embodiment 3

[0025] 5-chloro-N-(((5S)-2-oxo-3-(4-(3-oxomorpholin-4-yl)phenyl)-1,3-oxazolin-5-yl) Preparation of methyl)thiophene-2-carboxamide

[0026] Add 1.1792 g of S-(oxane-2-methyl)isoindoline-1,3-dione and 1.1 g of 4-(4-aminophenyl)-3-morpholinone to a round bottom flask, anhydrous methanol 4mL, distilled water 1mL, heated and stirred, reacted for 16h, after the reaction was completed, a solid was obtained after suction filtration, and the solid was dried in vacuum to obtain 5-chloro-N-(((5S)-2-oxo-3-(4-( 3-oxomorpholin-4-yl)phenyl)-1,3-oxazolin-5-yl)methyl)thiophene-2-carboxamide, the yield was 90%.

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 provides a preparation method and application of a rivaroxaban intermediate (S)-N-epoxy propyl phthalimide. The preparation method comprises the following steps: firstly, adding absolute ethyl alcohol into a reaction container accommodating phthalimide, dropwise adding a KOH methanol solution for 1h under a stirring condition, performing continuous stirring for 3h at the room temperature, performing filtration after the reaction is finished, leaching an obtained white solid by using the absolute ethyl alcohol, and drying the white solid; secondly, adding phthalimide potassium salt into (R)-epichlorohydrin, and performing heating reaction under a condition of oil bath at the temperature of 130 DEG C to obtain the (S)-N-epoxy propyl phthalimide. The method comprises only two process routes, the steps are simple, after conditions are optimized, the reaction is wild, the cost of raw materials is low, and the yield is high.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry and relates to a rivaroxaban intermediate, in particular to a preparation method of the rivaroxaban intermediate (S)-N-glycidyl phthalimide. Background technique [0002] Rivaroxaban is a new type of anticoagulant that can be directly taken orally. It directly inhibits the activated blood coagulation factor Xa, has an exact anticoagulant effect, does not require continuous monitoring, and has high safety. On September 15, 2008 and October 1, 2008, rivaroxaban was approved for marketing in Canada and the European Union respectively, and the trade name was Xarelto. On July 1, 2011, Bayer and Johnson & Johnson jointly announced that the anticoagulant drug rivaroxaban (English common name: Rivaroxaban, Chinese product name: Xarelto, English trade name: Xarelto) has been approved by the FDA for the prevention of Deep Vein Thrombosis (DVT). On November 4, 2011, rivaroxaban was approved by the US FD...

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): C07D405/06C07D413/14
CPCC07D405/06C07D413/14
Inventor 张胜
Owner ZHEJIANG TIANSHUN BIOTECH
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