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

Anti-hepatitis C Daclatasvir synthesis method

A technology of anti-hepatitis C daclatasvir and synthetic method, which is applied in the field of synthesis of anti-hepatitis C daclatasvir, can solve the problems of complex synthetic route and high cost of production raw materials, and achieve simple reaction, low cost of production raw materials, and step-by-step synthetic route little effect

Inactive Publication Date: 2017-02-22
上海步越化工科技有限公司
View PDF9 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The technical problem to be solved by the present invention is to provide a synthetic method of anti-hepatitis C daclatasvir, which solves the above-mentioned existing problems in the prior art such as high raw material cost and complex synthetic route

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
  • Anti-hepatitis C Daclatasvir synthesis method
  • Anti-hepatitis C Daclatasvir synthesis method
  • Anti-hepatitis C Daclatasvir synthesis method

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0025] Such as Figure 4 Shown, a kind of synthetic method of anti-hepatitis C daclatasvir, this synthetic method comprises the following steps:

[0026] (1) Using 4,4'-bis(2-chloroacetyl)biphenyl to condense with Boc-L-proline to generate ester;

[0027] (2) take above-mentioned ester and ammonium acetate ring closure, obtain imidazole;

[0028] (3) De-Boc the imidazole to obtain the hydrochloride;

[0029] (4) Take the hydrochloride and carry out Moc-L-valine condensation to obtain daclatasvir.

specific Embodiment approach 1

[0031] (1) Synthesis of esters

[0032] Stage a. Put 4,4'-bis(2-chloroacetyl)biphenyl (7.5g, 24.4mmol), Boc-L-proline (10.5g, 48.8mmol) and acetonitrile (70mL) into the reaction flask , add diisopropylethylamine DIPEA (6.5g, 50mmol);

[0033] Stage b. Heat up to 25°C (temperature range is 25-82°C), stir for 36 hours, the reaction is completed, the reaction solution is concentrated under reduced pressure, and replaced with toluene solution (140mL);

[0034] Stage c, washing twice with saturated sodium chloride (70 mL), concentrating toluene to obtain an oily foamy solid, namely the desired ester (15.6 g, yield 96.3%).

[0035] (2) Synthesis of imidazole

[0036] Add ester (15.6g, 23.5mmol) and 95mL toluene to the reaction flask, add ammonium acetate (30g, 389mmol), heat up to 95°C (temperature range is 95-100°C), and react for 15 hours;

[0037] Cool down to 60°C, slowly add saturated aqueous sodium bicarbonate solution, adjust the pH to 7 (PH range 7-8);

[0038] Layer at ...

specific Embodiment approach 2

[0049] (1) Synthesis of esters

[0050] Stage a. Put 4,4'-bis(2-chloroacetyl)biphenyl (7.5g, 24.4mmol), Boc-L-proline (10.5g, 48.8mmol) and acetonitrile (70mL) into the reaction flask , add diisopropylethylamine DIPEA (6.5g, 50mmol);

[0051] Stage b: heat up to 65°C (temperature range is 25-82°C), stir for 8 hours, the reaction is completed, the reaction solution is concentrated under reduced pressure, and replaced with toluene solution (140mL);

[0052] Stage c, washing twice with saturated sodium chloride (70 mL), concentrating toluene to obtain an oily foamy solid, namely the desired ester (15.6 g, yield 96.3%).

[0053] (2) Synthesis of imidazole

[0054] Add ester (15.6g, 23.5mmol) and 95mL toluene to the reaction flask, add ammonium acetate (30g, 389mmol), heat up to 97°C (temperature range is 95-100°C), and react for 15 hours;

[0055] Cool down to 60°C, slowly add saturated aqueous sodium bicarbonate solution, and adjust the pH to 7.3 (pH range 7-8);

[0056] Laye...

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 an anti-hepatitis C Daclatasvir synthesis method. The anti-hepatitis C Daclatasvir synthesis method comprises the following steps that 1, 4,4'-di(2-chloracetyl) biphenyl and Boc-L-proline perform condensation to generate ester; 2, the ester and ammonium acetate perform ring closure to obtain imidazole; 3, Boc is removed from the imidazole to obtain hydrochloride; 4, the hydrochloride is taken for Moc-L-valine condensation to obtain Daclatasvir, wherein in the step 1, a solvent is acetonitrile, and an acid-binding agent is diisopropylethylamine. By the adoption of the anti-hepatitis C Daclatasvir synthesis method, the preparation raw materials are low in cost, synthetic route steps are few, reaction is simple, and popularization and application are promoted.

Description

technical field [0001] The invention belongs to the field of chemical medicines, and in particular relates to a synthesis method of anti-hepatitis C daclatasvir. Background technique [0002] Daclatasvir (DAKLINZA) is a hepatitis C virus (HCV) NS5A inhibitor indicated for use with sofosbuvir for the treatment of chronic HCV genotype 3 infection. Its application has attracted people's attention, thus putting forward higher requirements for the production and synthesis method of daclatasvir. [0003] WO2008021927, WO2009020825, WO2009020828, WO2012048421, US20090068140 and US20100158862 have reported the synthesis method of daclatasvir, so far there are three synthesis methods of the drug. The first method: using p-bromoacetyl bromide as the starting material, first condense with Boc proline, then close the ring with ammonium acetate, and then prepare a boronate ester for coupling, finally remove Boc protection, and combine with Moc- L-valine is condensed to obtain daclatasv...

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): C07D403/14
CPCC07D403/14
Inventor 周盛峰冯志勇宋斌陈龙
Owner 上海步越化工科技有限公司
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