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

Process for the preparation of S-(+)-clopidogrel by optical resolution

A clopidogrel, optical separation technology, applied in organic chemistry, blood diseases, extracellular fluid diseases, etc., can solve problems such as difficult crystallization and purification

Inactive Publication Date: 2009-01-14
SK CHEM CO LTD
View PDF7 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0025] However, the conventional method of using 4,5,6,7-tetrahydro[3,2-c]thienopyridine of the formula (r) in Scheme 4 according to Scheme 4 has the disadvantage of having a low melting point and being easily soluble in organic Disadvantages of difficult purification by crystallization in solvents

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
  • Process for the preparation of S-(+)-clopidogrel by optical resolution
  • Process for the preparation of S-(+)-clopidogrel by optical resolution
  • Process for the preparation of S-(+)-clopidogrel by optical resolution

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Example 1: Synthesis of diastereomeric salts (4) from the racemic carboxylic acid (2a) of clopidogrel

[0048] 3.078 grams (10 mmol) of the racemic carboxylic acid (2a) of clopidogrel and 3.47 grams (10 mmol) of 85% (+)-cinchonine were put into a 250 milliliter flask, and by adding 100 milliliters of ethanol thereto: acetonitrile (1 : 2) to dissolve it completely. After the resulting solution was shaken at room temperature for 18 hours, the formed precipitate was filtered under reduced pressure and then vacuum dried at room temperature to obtain 1.74 g of the diastereomeric salt (4) as a white solid.

[0049] Theoretical yield 58%; optical purity 98.9% (HPLC); 1 H NMR (300MHz, DMSO-d 6 )δ8.85(d, 1H, J=4.5Hz), 8.28(d, 1H, J=8.1Hz), 8.02(dd, 1H, J=8.1Hz, 1.2Hz), 7.24-7.76(m, 8H) , 6.74(d, 1H, J=5.1Hz), 6.01-6.13(m, 1H), 5.58(d, 1H, J=5.1Hz), 5.14(d, 1H, J=9.3Hz), 5.09(s , 1H), 4.64(s, 1H), 3.56-3.73(m, 2H), 3.25-3.32(m, 2H), 2.66-2.90(m, 7H), 2.28-2.34(m, 1H), 1.95-2....

Embodiment 2

[0050] Example 2: Synthesis of diastereomeric salts (4) from the racemic carboxylic acid (2a) of clopidogrel

[0051] 3.078 grams (10 mmol) of the racemic carboxylic acid (2a) of clopidogrel and 1.735 grams (5 mmol) of 85% (+)-cinchonine were put into a 250 milliliter flask, and by adding 100 milliliters of ethanol thereto: acetonitrile (1 : 2) to dissolve it completely. After shaking the resulting solution at room temperature for 18 hours, the precipitate thus formed was filtered under reduced pressure and then dried under vacuum at room temperature to obtain 2.42 g of the diastereomeric salt (4) as a white solid.

[0052] Theoretical yield 80%; optical purity 99.8% (HPLC)

Embodiment 3

[0053] Example 3: Synthesis of diastereomeric salts (4) from the racemic carboxylic acid (2a) of clopidogrel

[0054] The racemic carboxylic acid (2a) of 3.078 grams (10mmol) clopidogrel and 3.078 grams (10mmol) 85% (+)-cinchonine are put into 250 milliliters flasks, and by adding 100 milliliters of ethanols wherein: acetone (1 : 2) to dissolve it completely. After shaking the resulting solution at room temperature for 18 hours, the precipitate thus formed was filtered under reduced pressure and then dried under vacuum at room temperature to obtain 2.54 g of the diastereomeric salt (4) as a white solid.

[0055] Theoretical yield 84%; optical purity 99.8% (HPLC)

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 present invention relates to a process for the preparation of S-(+)-clopidogrel by an optical resolution and, more particularly, to a process for the preparation of S-(+)-clopidogrel represented by the following formula 1 with high optical purity by converting a clopidogrel racemic carboxylic acid into a diastereomeric salt using a (+)-cinchonine for optical resolution, extracting an S-(+)-clopidogrel carboxylic acid from the diastereomeric salt using a suitable solvent under an acidic condition and then reacting the S-(+)-clopidogrel carboxylic acid with methanol.

Description

technical field [0001] The present invention relates to a method for preparing S-(+)-clopidogrel by optical resolution, more particularly, a method for preparing S-(+)-clopidogrel represented by the following formula 1 with high optical purity, by using (+)-Cinchonine is optically resolved to convert the racemic carboxylic acid of clopidogrel into diastereomeric salts. Under acidic conditions, use a suitable solvent to extract S-(+)- from the diastereomeric salts. Clopidogrel carboxylic acid, followed by reaction of S-(+)-clopidogrel carboxylic acid with methanol. [0002] [Formula 1] [0003] Background technique [0004] The chemical name of S-(+)-clopidogrel represented by formula 1 is (+)-(S)-α-(o-chlorophenyl)-6,7-dihydrothieno[3,2-a]pyridine - 5-(4H)-Methyl acetate, which is known as an effective therapeutic agent for diseases of the vascular system, for the treatment of peripheral arterial diseases such as cerebral apoplexy, thrombus, embolism, etc., and coronary...

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): C07D495/04C07D513/08C07D498/02A61P7/02A61P9/10
CPCC07D495/04A61P7/02A61P9/00A61P9/10
Inventor 金南镐李镇英金载善李男奎
Owner SK CHEM 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