Patent ID: 6458963
Filing Date: 2002-10-01
Classification: A61P,C07D,Y02P

Abstract:
A process for the preparation of eprosartan, a compound of formula (I): or a pharmaceutically acceptable salt thereof, which process comprises the steps of:(i) treating a compound of formula (II): with base, followed by reaction with a regioselective nitrogen-protecting reagent;(ii) reacting the compound of formula (III): wherein R1 is a nitrogen protecting group either consisting of (1) an ethylene bridge connecting the nitrogen to an electron-withdrawing group, selected from the group consisting of an ester (COORâ€³, where Râ€³=C1-4alkyl), acid, carbonyl, nitrile, sulfone, and sulfoxide, or (2) a methylene bridge connecting the nitrogen to a pivalate, 2-(trimethylsily)ethoxy, methoxy, tert-butoxy, or benzyloxy, with a compound of formula (IV): wherein Râ€² is C1-4alkyl, in the presence of a catalyst; and(iii) reacting the compound of formula (V): wherein Râ€² and R1 are as defined above, with a compound of formula (VI): wherein Râ€²â€³ is C1-4alkyl and X is halo or OR*, in which R* is CH3SO2- or p-CH3C6H4SO2-, at elevated temperatures;and thereafter hydrolyzing the Râ€² and Râ€²â€³ ester groups and removing the Nâˆ’3 protecting group, and optionally forming a pharmaceutically acceptable salt.