Process for manufacture of telmisartan

摘要

A process for preparing telmisartan by reacting 2-n-propyl-4-methyl-6-(1′-methylbenzimidazol-2′-yl)benzimidazole with a compound of formula (IV);
wherein Z is a leaving group, to obtain the compound 2-cyano-4′-[2″-n-propyl-4″-methyl-6″-(1′″-methylbenzimidazol-2′″-yl)benzimidazol-1″-ylmethyl]biphenyl, and subsequently hydrolyzing the nitrile function to obtain the acid function.

主权项

1. A process for preparing telmisartan, comprising:
(a) reacting 2-n-propyl-4-methyl-6-(1′-methylbenzimidazol-2′-yl)benzimidazole (I):with a compound of formula (IV):wherein Z is a leaving group, in a first solvent selected from methylene chloride, diethyl ether, tetrahydrofuran, dioxane, dimethylsulfoxide, dimethylformamide, dimethylacetamide, dimethylformamide/tert-butanol, dimethylacetamide/tert-butanol, toluene, benzene or a mixture thereof, to obtain a compound 2-cyano-4′-[2″-n-propyl-4″-methyl-6″-(1′″methylbenzimidazol-2′″-yl)-benzimidazol-1″-ylmethyl]biphenyl (V):and
(b) hydrolyzing the nitrile function of compound (V) obtained from step (a) into the acid function in a second solvent selected from water, methanol, ethanol, n-propanol, isopropanol, tetrahydrofuran, dioxane, ethylene glycol, propyleneglycol, diglyme, dimethylsulfoxide, diethylene glycol monomethyl ether or a mixture thereof, in the presence of a base and at a temperature between 80° C. and 200° C., to obtain telmisartan.