Clopidogrel Bisulfate Synthesis Process Research

Cardiac and cerebrovascular disease is a common disease. It is well recognized that antiplatelet agent is effective in the prevention and treatment of thrombosis. Clopidogrel hydrogen sulfate, which can irreversibly inhibit platelet aggregation, is one of thieno pyridine derivatives. It was developed by Sanofi, and was marketed as Plavix in 1998. It has been used clinically for the treatment of arterial thrombotic diseases such as myocardial infarction and stroke.In this thesis, the formation and feature of the thrombus was introduced briefly and the research progress of antiplatelet agent was reviewed. The pharmacology and research information of clopidogrel was also eludidated in detail. The synthetic method of clopidogrel hydrogen sulfate was finally determined and the reaction conditions were optimized. Starting from 2-thiopheneethanol, polymorph I of clopidogrel hydrogen sulfate was prepared by esterification, substitution, followed by cyclization and salification. The total yield was 68%, which was higher than literatures (40%-50%). This process has established the foundation for the large-scale synthesis.The structure of the target molecule and some intermediates were determined by IR, 1H-NMR, 13C-NMR, MS and X-ray powder diffractogram.