Patent ID: 8716476
Filing Date: 2014-05-06
Classification: C07D

Abstract:
1. A process for preparing alfuzosin or a salt thereof comprising: (a) condensing 4-amino-2-chloro-6,7-dimethoxyquinazoline (II) with 3-methylaminopropionitrile (III) in the presence of (i) a polar aprotic solvent selected from the group consisting of: diglyme, dimethyl formamide, hexamethylphosphoramide, and mixtures thereof, or (ii) a mixture of a polar aprotic solvent in combination with t-butanol, to form N-(4-amino-6,7-dimethoxyquinazol-2-yl)-N-methyl-2-cyanoethylamine (IV), wherein the condensation reaction is carried out in the absence of a base; (b) hydrogenating the N-(4-amino-6,7-dimethoxyquinazol-2-yl)-N-methyl-2-cyanoethylamine (IV) using a hydrogenating agent under a pressure of less than 10 kg/cm and (c) converting tetrahydrofuroic acid (VI) to an intermediate form (VII) and condensing the intermediate form (VII) with the N-(4-amino-6,7-dimethoxyquinazol-2-yl)-N-methylpropylenediamine (V) or with the acid addition salt thereof to yield alfuzosin base, and optionally converting alfuzosin base to a salt of alfuzosin, wherein R is: (i) a halo group; (ii) OR wherein the silyl group is nitrogen bonded to the oxygen of the OR or (ii) asparagine, wherein the process is carried out without isolating the intermediate of formula (VII).