Process for synthesizing prasugrel

Abstract

The invention provides a novel process for synthesizing prasugrel. In the process, a prasugrel intermediate addition salt having a ketone-enol tautomer structure is used for preparing the prasugrel, so that the process has the advantages of easy synthesis, easy storage and convenient preparation of prasugrel. Due to the use of the intermediate addition in the preparation of the prasugrel, the purity requirement on synthesis raw materials is lowered, the time-consuming and labor-consuming process of column chromatography separation of the intermediates is eliminated, the separation purification efficiency is improved, and the process is quite suitable for the industrialized production of the prasugrel.

Description

technical field The present invention relates to chemical synthesis, in particular to the preparation of platelet inhibitor prasugrel. Background technique Thienopyridines such as ticlopidine and clopidogrel have been used to treat thrombosis and related diseases. As a new generation of thienopyridine oral antiplatelet drugs, prasugrel has also been launched under the trade name Effient. The structural formula of prasugrel, such as III, is an adenosine diphosphate (ADP) receptor antagonist, which belongs to the prodrug, which itself does not have activity and is effectively converted into its active metabolite R-138727 in vivo; R- 138727 reduces the dependence on cytochrome P-450 enzymes, and rapidly, specifically, and irreversibly binds to the purine base receptors of platelet P2Y12, inhibiting ADP-regulated platelet activity and aggregation. Patent EP0542411 first disclosed tetrahydrothienopyridine derivatives including prasugrel, and later many patents related to the s...

AI Technical Summary

Problems solved by technology

Exist time-consuming and laborious in these preparation processes, be unfavorable for the deficiency of industrialization: (1) when synthesizing this key intermediate (IV), generally require the compound V purity of preparation to be higher, need column chromatographic separation during preparation time-consuming and laborious, not suitable for large-scale industrialization Production, if the temperature of preparing compound V by rectification is too high, it is uneconomical to easily polymerize and lose a large amount of compound V, and it is easy to fail; (2) after the key intermediate compound IV is prepared, it is generally time-consuming and laborious to separate by column chromatography, and the loss is relatively large many

Images