US 2011/0087028 A1Published application

Method for preparing clopidogrel and its derivatives

AssigneeEnzytech, Inc.

InventorsSoon Ook Hwang, Young Jin Kim

Life of this patent

Estimating the term…

Loading patent…

Abstract

The present invention relates to a method for preparing Clopidogrel and its derivatives. More particularly, the present invention is a method for preparation of (S)-2-Clopidogrel and its derivatives, which are active inhibitors of platelet aggregation, from an optically active (S)-2-chlorophenyl glycine alkyl ester through hydrolysis of racemic 2-chlorophenylglycine alkyl esters using an enzyme. The present invention employs a simple procedure to prepare Clopidogrel and its derivatives. Because no chiral resolving agents are used except for a small amount of enzyme, the cost of preparation can be reduced. In addition, the present invention is suitable for synthesizing highly optical-active Clopidogrel and its derivatives on a large scale by using optically active (S)-2-chlorophenylglycine alkyl ester obtained in high yield as an intermediate, and is also environmentally friendly since no highly toxic reagents are employed.

Claims7

Dependent claims

A method for preparing (S)-Clopidogrel represented by Chemical Formula 1, or derivatives or salts thereof, comprising the steps of:

(a) subjecting a racemic 2-chlorophenylglycine alkyl ester compound represented by Chemical Formula 9 to enzymatic hydrolysis to obtain an optically active compound represented by the following Chemical Formula 10;
(b) reacting the optically active compound represented by Chemical Formula 10 with a compound represented by the following Chemical Formula 11 to obtain a compound represented by the following Chemical Formula 12;
and
(c) carrying out cyclization of the compound represented by Chemical Formula 12 with a formylating agent in the presence of an acid:
wherein R1 is H, substituted or non-substituted C1-C8 alkyl, substituted or non-substituted C1-C8 alkenyl, benzyl or C3-C6 cycloalkyl;
and X is a halogen atom selected from the group consisting of fluorine (F), chlorine (Cl), bromine (Br) and iodine (I) or —OSO2R2 (wherein R2 is substituted or non-substituted C1-C8 alkyl, substituted or non-substituted aryl substituted or non-substituted arylalkyl, substituted or non-substituted heteroaryl or substituted or non-substituted nheteroarylalkyl).

3 more elements

Dependencies are inferred from the claim text.