Preparation method of sofosbuvir

A technology of sofosbuvir and methyl, which is applied in the field of preparation of sofosbuvir, can solve the problems of difficult raw materials, complex docking or hydrolysis process, etc., and achieve the effect of easy raw materials, low cost and few reaction steps

Active Publication Date: 2017-04-19
常州市勇毅生物药业有限公司
View PDF4 Cites 9 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The above-mentioned synthetic methods have the problems that the raw materials are not easy to obtain in different degrees, and the docking or hydrolysis process in the reaction is complicated.

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
  • Preparation method of sofosbuvir
  • Preparation method of sofosbuvir
  • Preparation method of sofosbuvir

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Add 300ml of anhydrous methanol to a 500ml single-necked bottle, cool to 0-5°C in an ice bath, slowly add 5.2g (20mol%) acetyl chloride dropwise, keep stirring for 20 minutes, add 50g of D-ribose, rise to room temperature and stir After 24 hours, the solvent was removed by concentration to obtain 55 g of white solid product methyl-β-D-nucleoside.

[0029] Add 50 grams of methyl-β-D-nucleoside, 500 milliliters of dichloromethane and 100 milliliters of anhydrous pyridine into a 1-liter reaction flask, cool down to 0°C, slowly add 97.5 milliliters of TIPDSCl dropwise, and use 10 Rinse the dropping funnel with a milliliter of dichloromethane, then rise to room temperature and stir for 3 hours, add 2M hydrochloric acid, separate layers, extract the aqueous layer with 200 ml of dichloromethane, combine the organic phases, wash with saturated brine twice, and dry over sodium sulfate , filtered, and concentrated to obtain 92 grams of the product methyl-3,5-O-(1,1,3,3-tetraisopr...

Embodiment 2

[0037] Add 300ml of anhydrous methanol to a 500ml single-necked bottle, cool to 0-5°C in an ice bath, slowly add 5.2g (20mol%) acetyl chloride dropwise, keep stirring for 30 minutes, add 50g of D-ribose, rise to room temperature and stir After 24 hours, the solvent was removed by concentration to obtain 55 g of white solid product methyl-β-D-nucleoside.

[0038] Add 50 grams of methyl-β-D-nucleoside, 500 milliliters of dichloromethane and 100 milliliters of anhydrous pyridine into a 1-liter reaction flask, cool down to 0°C, slowly add 97.5 milliliters of TIPDSCl dropwise, and use 10 Rinse the dropping funnel with a milliliter of dichloromethane, then rise to room temperature and stir for 3.5 hours, add 2M hydrochloric acid, separate layers, extract the aqueous layer with 200 ml of dichloromethane, combine the organic phases, wash with saturated brine twice, and dry over sodium sulfate , filtered, and concentrated to obtain 92 grams of the product methyl-3,5-O-(1,1,3,3-tetraiso...

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 technical field of medicine, in particular to a preparation method of sofosbuvir. The method adopts D-ribose as the starting material, and carries out esterification reaction, hydroxyl protection reaction, hydroxyl oxidation reaction, methylation reaction, fluorination reaction, docking reaction, hydrolysis, phosphate ester side chain connection and a series of reactions, thus finally obtaining the product sofosbuvir. The preparation method of sofosbuvir provided by the invention adopts D-ribose as the raw material, the raw materials are easily available and low in cost, and the one-step hydrolysis reaction adopted by the invention has few step, therefore the method is easy for industrialization.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a preparation method of sofosbuvir. Background technique [0002] Sofosbuvir (also translated as Sofosbuvir, English name Sofosbuvir, trade name Sovaldi) is a new drug developed by Gilead for the treatment of chronic hepatitis C. It was approved by the US Food and Drug Administration (FDA) on December 6, 2013. ) was approved for marketing in the United States, and was approved for marketing in EU countries by the European Medicines Agency (EMEA) on January 16, 2014. [0003] Chinese patent application 201410635081.2 discloses a preparation of sofosbuvir using uridine as a raw material through steps of etherification, oxidation, addition and condensation. [0004] Chinese patent application 201510052214.8 discloses a method for preparing high-purity sofosbuvir, using SF-2 raw material, deprotecting with MeNa, generating intermediate SF-1 and then connecting with phosphate side c...

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): C07H19/10C07H1/00
Inventor 潘勇夏晓丽
Owner 常州市勇毅生物药业有限公司
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