Synthesis Of3-(4-chlorobutyl)-5-cyano Indole-the Intermediates Of Antidepressants Vilazodone

This paper reviewed depression,the history of antidepressant drugs and mainlyintroduced a new antidepressant drug Vilazodone.In2011, Vilazodone has been approved bythe FDA as clinical drugs for the treatment of adults with severe depression. Vilazodone hasexcellent clinical efficacy, because it has the SSRI and5-HT1Aagonist double pharmacophore.Compared with conventional antidepressants, it has a faster onset, better selectivity andgreater efficacy. In view of its good prospects, the synthesis of3-(4-chlorobutyl)-5-cyanoindole were studied in this paper,which is a key intermediate to the synthesis of Vilazodone.Firstly, according to "indole-indoline-indole" synthesis of indole, indole and sodiumhydrogen sulfite were selected as starting materials, after the addition, N-acyl protection,bromination and deacylated finally synthesized5-bromo indole. But with cuprous cyanide ascyanide reagent, the next step failed to prepare5-cyano indole.According to the method of L-B indole synthesis, with methyl aniline as starting material,after N-acyl protection, nitration, diazotization, Sandmeyer cyano and reductive cyclizationfinally give the protected5-cyano indole.Then,5-cyano indole was selected as the substrate and4-chlorobutyryl chloride as theacylating agent, after Friedel-Crafts acylation reaction3-(4-chlorobutyryl)-5-cyano-indolewas finally synthesized.In this paper, the factors affecting the course of each step of reaction were discussed, therelevant mechanisms were analyzed, and the structures of the products and the intermediateswere confirmed by IR,1HNMR.