Patent ID: 8716476

Claim:
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 2 to form N-(4-amino-6,7-dimethoxyquinazol-2-yl)-N-methylpropylenediamine (V) and optionally converting the N-(4-amino-6,7-dimethoxyquinazol-2-yl)-N-methylpropylenediamine (V) to an acid addition salt thereof, wherein the hydrogenation is carried out in the presence of an alcohol and an aqueous ammonia solution; 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 1 wherein R 1 is a silyl group of the formula wherein the silyl group is nitrogen bonded to the oxygen of the OR 1 group, and wherein R′, R″ and R′″ are the same or different and are selected from hydrogen, optionally substituted C 1 -C 6 alkyl and optionally substituted C 2 -C 6 alkenyl; Y is selected from hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl and optionally substituted silyl of the formula —SiH 3 ; (iii) OR 2 wherein R 2 is a C 1 to C 4 alkyl group; or (iv) OR 3 , wherein R 3 is either (i) succinimide and intermediate form (VII) is intermediate ester (VIIc) or (ii) asparagine, wherein the process is carried out without isolating the intermediate of formula (VII).