A kind of synthetic method of ticagrelor

Abstract

The invention discloses a synthetic method of ticagrelor, which comprises the following steps: (a) using 6-halo-2-propylthio-8-azapurine as a raw material, in an alkali and an organic solvent, at room temperature , react with (1R,2S)-2-(3,4-difluorophenyl)cyclopropylcarbamate tert-butyl ester to obtain intermediate (II); (b) at room temperature, intermediate (II ) is dissolved in an organic solvent with compound (III), and reacts under the effect of triphenylphosphine and diethyl azodicarboxylate to obtain intermediate (IV); (c) intermediate (IV) in acid Under the action of deprotection, ticagrelor (I) was obtained. The method has the advantages of cheap and easy-to-obtain raw materials, low production cost, short reaction steps, mild reaction conditions, convenient post-treatment, high yield, and is more suitable for industrial production.

Description

A kind of synthetic method of ticagrelor technical field The invention belongs to the field of medicine synthesis, be specifically related to a kind of synthetic method of ticagrelor. Background technique Ticagrelor, belongs to cyclopentyl triazole pyrimidine family non-thiophene pyridine drugs, is developed by Astrazeneca company The first oral reversible P2Y12 receptor inhibitor. The drug was approved by the European Medicines Agency at the end of 2010, and in July 2011 It was approved by the U.S. Food and Drug Administration to reduce the incidence of thrombotic cardiovascular events in patients with acute coronary syndrome. 2012 In November, the drug obtained the import drug license issued by the State Food and Drug Administration and was officially launched in China. In the prior art, about the synthetic method of ticagrelor mainly has following several methods disclosed in relevant documents Case: 1. The preparation scheme disclosed in CN1128801C patent is:...

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Problems solved by technology

However, the fourth scheme has long reaction steps, the obtained intermediates are relatively complicated, and the post-processing is cumbersome, which is not conducive to industrial production.

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