Vilazodone can be prepared by two related ways: 1) The condensation of indole-5-carbonitrile (I) with 4-chlorobutyryl chloride (II) gives 3-(4-chlorobutyryl)-1H-indole-5-carbonitrile (III), which is reduced with diborane, yielding 3-(4-chlorobutyl)-1H-indole-5-carbonitrile (IV). Reaction of compound (IV) with 5-(1-piperazinyl)benzofuran-2-carboxylic acid (V) affords the expected 1,4-disubstituted piperazine (VI). Finally, the carboxy group of (VI) is converted into the target carboxamide by reaction with 2-chloro-1-methylpyridinium methanesulfonate (CMPM) and ammonia gas. 5-(1-Piperazinyl)benzofuran-2-carboxylic acid (V) is obtained by cyclization of 5-aminobenzofuran-2-carboxylic acid (VII) with bis(2-chloroethyl)amine (VIII). 2) The hydrogenation of 5-nitrobenzofuran-2-carboxylic acid ethyl ester (IX) with H2 and Raney nickel in MeOH gives the corresponding 5-aminobenzofuran compound (X), which is cyclized with bis(2-chloroethyl)amine (VIII) in dichloromethane to afford 5-(1-piperazinyl)benzofuran-2-carboxylic acid ethyl ester (XI). Reaction of compound (XI) with di-tert-butyl dicarbonate in THF provides the protected amine compound 5-[4-(tert-butoxycarbonyl)-1-piperazinyl]benzofuran-2-carboxylic acid ethyl ester (XII), which first is reacted with formamide and sodium alkoxide in N-methylpyrrolidone to provide the corresponding amide (XIII) and then is deprotected by treatment with HCl/MeOH to give 5-(1-piperazinyl)benzofuran-2-carboxamide (XIV). Finally, amide (XIV) is condensed with 3-(4-chlorobutyl)-1H-indole-5-carbonitrile (IV).