Preparation process of clopidogre and its salt

Abstract

The present invention provides one kind of compound with anticoagulant effect, and is especially new preparation process of clopidogrel and its pharmaceutical salt. The preparation process includes the following four steps: 1. resolving recemized methyl o-chlorophenyl glycinate to obtain (+)-methyl o-chlorophenyl glycinate and (-)-methyl o-chlorophenyl glycinate; 2. recemizing (-)-methyl o-chlorophenyl glycinate to obtain recemized (-)-methyl o-chlorophenyl glycinate; 3. repeating the steps 1 and 2; and 4. preparing clopidogrel with (+)-methyl o-chlorophenyl glycinate obtained in the step 1 and preparing the obtained clopidogrel into corresponding salt. The process of the present invention has simple path, short circulating period, low cost, high product purity, less toxic side effect and corrosion to the production apparatus.

Description

Technical field: [0001] The invention relates to a preparation method of a compound, especially a method for preparing clopidogrel and its pharmaceutically acceptable salt. Background technique: [0002] Clopidogrel [Methyl S(+)-2-(2-chlorophenyl)-2-(4,5,6,7-tetrahydrothiophene[3,2-c]pyridine-5)acetate], The structural formula is as follows: [0003] [0004] Clopidogrel is a platelet aggregation inhibitor that selectively inhibits the binding of adenosine diphosphate (ADP) to its receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb / IIIa complex, thus inhibiting Platelet aggregation. Clopidogrel was first jointly developed by Japan's Daiichi Pharmaceutical and France's Sanofi (Sanofi), and was launched in the United States in 1998. [0005] At present, many patents have reported the preparation methods of clopidogrel and its salts. Patent US4847265 discusses the preparation process of (S)-(+)-clopidogrel. Patent US4529596 also reports the pre...

AI Technical Summary

Problems solved by technology

[0009] Although the prior art proposes a method that can recycle the isomers or derivatives of the reaction intermediate substance I, this method uses thionyl chloride to reflux for 12 hours to achieve racemization. In actual production, thionyl chloride The decomposition of sulfone will produce a large amount of hydrochloric acid and sulfur dioxide gas, which will corrode the reactor and affect the health of workers. Therefore, it is necessary to carry out tail gas treatment, increase equipment, consume labor and energy, and increase the burden of environmental protection.

In addition, in the prior art, after the racemization reaction, the optical rotation of the product is -5°~5°, the racemization is not complete, and complete racemization cannot be achieved.

Images