One pot process for the preparation of telmisartan

摘要

A process for the preparation of bromine free telmisartan in one pot starting from 2-cyano-4′-methyl biphenyl. The process uses raw materials which are readily available to yield telmisartan, its salts and derivatives thereof, which are bromine free and potentially less genotoxic, since there is no bromine atom in any of the raw materials.;The process can also be carried out in multiple steps by isolation of the intermediate compounds. The intermediate compound 4-chloromethyl-2′-cyanobiphenyl can also be used for the preparation of irbesartan and other sartans.

主权项

1. A process for preparing bromine free telmisartan in a one pot comprising:
(a) chlorination of 2-cyano-4′-methyl biphenyl, a compound of Formula 1 using chlorine gas in a first solvent selected from a chlorinated hydrocarbon to give 4-chloromethyl-2′-cyanobiphenyl, a compound of Formula 2 (b) the compound of Formula 2 is reacted with 2-n-propyl-4-methyl-6-(1′methylbenzimidazol-2′-yl)benzimidazole, a compound of Formula 3 in a second solvent selected from an aromatic hydrocarbon and a ketone at a temperature between 50° C. to 110° C. in the presence of a base and a phase transfer catalyst to yield 2-cyano-4′-(2″-n-propyl-4″-methyl-6″-(1′″-methylbenzimidazol-2″-yl) benzimidazol-1″-ylmethyl) biphenyl, a compound of Formula 4 (c) hydrolysis of the cyano group of the compound of Formula 4 in the presence of a third solvent, which is an alcohol, in the presence of a base at a temperature between 110° C. to 145° C. followed by neutralization with an acid to yield telmisartan, a compound of Formula 5, wherein in step (a) the chlorination of the compound of Formula 1 is carried out using chlorine gas, without a free radical initiator or a catalyst to give the compound of Formula 2.