Research On The Synthesis Of5-(4’-(4-(5-cyano-1h-indole-3-yl)Butyl)Piperazin-1-yl)-benzofuran-2-carboxamide

5-(4-(4’-(5-cyano-1H-indole-3-yl)butyl) piperazin-1-yl)-benzofuran-2-carboxamide is the active pharmaceutical ingredientof vilazodone (new antidepressant drug),whose productionrequires two key intermediates, i.e.,5-piperazinyl-benofuran-2-carboxylate hydrochloride and3-(4’-chlorobutyryl)-5-cyano-indole.a novel synthetic route is designed to synthesize3-(4’-chlorobutyryl)-5-cyano-indole, i.e.,5-cyanoindole reacted with p-toluenesulfonic chloride to form1-tosyl-lH-indole-5-carbonitrile, which reacted with4-chlorobutyryl chloride via Friedel-Crafts acylation to form3-(4’-chlorobutanoyl)-l-tosyl-lH-indole-5-carbonitrile in the present of anhydrous aluminum chloride. The reduction of carbonylin3-(4’-chlorobutanoyl)-1-tosyl-lH-indole-5-carbonitrile was made with NaBH4in TFA to afford3-(4’-chlorobutyl)-1-tosyl-lH-indole-5-carbonitrile, which directly reacted with5-piperazinyl benzofuran-2-carboxylate hydrochloride, to generate5-(4’-(4-(5-cyano-1H-indole-3-yl)butyl) piperazin-1-yl)-benzofuran-2-carboxamide follow by deprotection, esterolysis reactions and amination reaction. The overall yield of six steps of reactions is50.37%. Another advantage of the above synthetic route is thatthe product of each step of reaction was purified by recrystallisation before subsequent reaction and obviated the use of silica gel column chromatography to purify the reaction intermediate as literature report. The chemical structures of the product of each step of reaction were characterized by’HNMR and Ms, and purity was characterized by HPLC.The mechanism of each reaction was discussed, the effect of several factors on the reaction results was observed, and some reaction conditions were optimized in order to obtain the desired research results.