Synthesis Of Prasugrel And The Analogs

Prasugrel is a new generation of oral anti-platelet aggregation drug with high oral bioavailability,faster onset,and can be removed from the loading dose administration, developed by Lilly and Sankyo,used to treat atherosclerosis and acute coronary syndrome (ACS).Based on the analysis of the synthesis route discribled in the references,we provided a novel method suitable for preparation of prasugrel in which all materials and reagents used are cheap and commercial available.2-Fluorobenzyl bromide in the paper was used as raw material,undergone Grignard reaction,transesterification,oxidation and so on, produced key intermediate 2-cyclopropyl-1-(2-fluophenyl)-2-carbonyl ethyl mesylate, reacted with 2-oxo-2,4,5,6,7,7a-hexahydrothieno[3,2-c]pyridine hydrochloride in the base conditions,after acylating,we got the final product.In the process,3 new compounds are involved.We also did some chemical modification of 2-acetoxy-4,5,6,7-tetrahydrothieno [3,2-c]pyridine nucleus in order to find a better anti-platelet aggregation activity of compounds.We modified position 5 on thienopyridine nucleus.Carbamate was introduced to position 5,thus 10 new thienopyridine derivatives were synthesized and their structures were confirmed by MS and ~1H-NMR.