Alternative Approach to Synthesis of 3-(4-chloro butyl)-1H-indole-5-carbonitrile: A Key Intermediate of Vilazodone Hydrochloride, an Antidepressant Drug

Abstract

An alternative and efficient telescopic approach to the synthesis of 3-(4-chloro butyl)-1H-indole -5-carbonitrile (2), a key intermediate in the synthesis of vilazodone hydrochloride (1), is described.

Expedient method for acylation of amines, alcohols and thiol using trimethylsilyl acetate

“…Moreover, acetylation of bioactive molecules, hetero atom constituted compounds such as natural phenols, confers enhanced lipophilicity, eventually leading to an improved bioactivity. [5][6][7][8][9][10][11][12] There are several other methods have been reported for acylation of amines, alcohols and thiols which include 4-(Dimethyl amino)pyridine (DMAP) [13][14] , CoCl21 15 , ZnCl2 16 , ZnO 17,18 , CeCl3 19 , ZrOCl2.8H2O 20 , molecular iodine [21][22] , 3-nitrobenzeneboronic acid, 23 La(NO3)3.6H2O, 24 P2O5/Al2O3, 25 NiCl2, 26 Co(II)salen-complex, 27 melamine trisulfonic acid, 28 Sn(TPP)(BF4)2, 29 alkylorthoformate-ZnCl2-Ac2O, 30 vanadium (IV) tetraphenylporphyrin, 31 [Ti IV (salophen)(OTf)2], 32 N-acyl 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) tetraphenylborate salts 33 , iron(III) tosylate, 34 Al(HSO4)3, 35 NbCl5, 36, Zn(Otf)2 37. Recently, metal triflates, other metal salts, [38][39][40][41][42] and ionic liquids etc. [43][44][45][46][47][48] (Scheme 1).…”

Practical and Scalable Manufacturing Process for a Novel Dual-Acting Serotonergic Antidepressant Vilazodone

“…Route 3 is a brand new synthesis method, which uses low-cost ε-caprolactone as the raw material to obtain the target compound vilazodone (Scheme ) through four steps, with a total yield of 14.2%. − ε-Caprolactone is much cheaper than 5-cyanoindole. However, the reactive conditions are relatively harsh, and the reaction yield is low.…”