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

Synthetic method of sofosbuvir intermediate

A synthesis method and compound technology, applied in chemical instruments and methods, preparation of sugar derivatives, sugar derivatives, etc., can solve problems such as large waste water, and achieve the effects of simple industrial operation, reducing the loss of dissolution in water, and improving yield

Inactive Publication Date: 2015-11-18
JIANGSU COBEN PHARMA CO LTD
View PDF7 Cites 10 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The pH buffering by the sodium citrate system can reduce the hydrolysis of chlorides, but this process produces a large amount of waste water

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 sofosbuvir intermediate
  • Synthetic method of sofosbuvir intermediate
  • Synthetic method of sofosbuvir intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1 Preparation of (2'R)-N-benzoyl-2'-deoxy-2'-fluoro-2'-methylcytidine-3',5'-dibenzoate

[0027] -25~-15 ℃ temperature, under the protection of nitrogen, 100 grams of red aluminum (70% content), drop into the mixed solution of 35 grams of toluene and 35 grams of trifluoroethanol, after dropping, warm up to room temperature and stir for 1 hour, set aside .

[0028] -20~-15 ℃ temperature, under nitrogen protection, 74.4 grams (0.2mol) 3,5-dibenzoyl-2-deoxy-2-fluoro-2 methyl-D-ribose-γ-lactone (compound III), 150 grams of toluene was added in the reaction flask, slowly dripped into 148 grams of the modified red aluminum solution of the previous step, dripped in about 3 hours, and kept warm for 30 minutes after the dripping, TLC tracked the disappearance of the raw material point, and obtained compound IV Toluene solution.

[0029] To the reaction solution in the previous step, add 2.9 g (0.04 mol) of N,N-dimethylformamide (DMF) at a temperature of -20 to -15 ° C, ...

Embodiment 2～12

[0034] Referring to Example 1, different SOCl 2 , DMF consumption, the reaction yield when thionyl chloride dripping temperature is different, chlorination temperature is different (except chlorination process, feed intake and other treatment methods are identical with embodiment 1), reaction condition and result are as shown in table 1 below :

[0035] Table 1

[0036]

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 a synthetic method of sofosbuvir intermediate-(2'R)-N- benzoyl-2'-deoxy-2'-fluoro-2'-methylcytidine-3',5'-dibenzoate represented by a formula (I) (shown in the specification). The synthetic method comprises the steps of generating a reduction product compound IV of a compound III from the compound III in the presence of modified red aluminum, generating a chlorinated compound V from the compound IV through sulfoxide chloride chlorination under the catalysis of N,N-dimethylformamide, after separating organic materials and aluminum salt from the compound V, directly condensing the compound V with a compound VI N-benzoyl-O-(trimethylsilyl)cytosine, and carrying out hydrolysis by virtue of an acetic acid solution, so as to obtain (2'R)-N- benzoyl-2'-deoxy-2'-fluoro-2'-methylcytidine-3',5'-dibenzoate represented by the formula (I). The synthetic method has the advantages of high yield, convenience in operation and suitability in industrial production.

Description

technical field [0001] The invention relates to a synthesis method of (2'R)-N-benzoyl-2'-deoxy-2'-fluoro-2'-methylcytidine-3',5'-dibenzoate. Background technique [0002] Sofosbuvir (compound II), also known as: Sofosbuvir, English name: Sofosbuvir, is a new drug developed by Gilead for the treatment of chronic hepatitis C, approved by the U.S. Food and Drug Administration ( FDA) approved for marketing in the United States, and on January 16, 2014, it was approved for marketing in EU countries by the European Medicines Agency (EMEA). The drug is the first drug that can safely and effectively treat certain types of hepatitis C without combining interferon, and the market capacity is huge. In the sofosbuvir synthesis process, the commonly used route in industry is as follows (references: [1] J.Org.Chem., 2009, 74, 6819-6824; [2] US2010056770 (2010); [3] US2103324709 ( 2013)): [0003] [0004] Sofosbuvir key intermediate (2'R)-N-benzoyl-2'-deoxy-2'-fluoro-2'-methylcytidi...

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): C07H19/073C07H1/00
Inventor 游金宗蒋善会郭红强何牮石蔡金元
Owner JIANGSU COBEN PHARMA CO LTD
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