Dimethylformamide → Vilazodone methyl ester

Participants

Reaction Conditions

Reaction Steps

Methyl 5-(1-piperazinyl)benzofuran-2-carboxylate (5 g), 3-[4-(p-toluenesulfonyloxy)butyl]-1H-indole-5-carbonitrile (6.3 g) and triethylamine (7 ml) were added to dimethylformamide (6.3 ml) and the resulting mixture was heated to 77-82° C., followed by stirring for 45 minutes at the same temperature. Water (30 ml) was added to the reaction mass and then stirred for 5 minutes at 25-30° C. The separated aqueous layer was extracted two times with toluene (2×250 ml). The resulting organic layers were combined and then washed two times with water (2×250 ml) and then distilled off the solvent under vacuum to produce 9.5 g of the titled compound as a residue. Methanol (47.5 ml) was added to the residue at 25-30° C. and then stirred for 30 minutes at the same temperature. The separated solid was filtered, washed with chilled methanol (10 ml) and then dried the material at 70-75° C. to produce 6 g of Methyl 5-[4-[4-(5-cyanoindol-3-yl)butyl]piperazin-1-yl]benzofuran-2-carboxylate (Purity by HPLC: 99%; Yield: 76.9%).

Provenance & Evidence