N-methyl-2-pyrrolidone → 2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile

Participants

Reaction Conditions

Reaction Steps

An NMP solution (150 mL) of N-[4-chloro-2-(1-propyn-1-yl)-3-(trifluoromethyl)phenyl]-2,2-dimethylpropanamide (10 g, 31.5 mmol) was treated with CuCN (11.3 g, 126 mmol) and the resulting mixture was heated at 195° C. for 90 h. Two reactions were carried out simultaneously. The combined dark brown reaction mixture was poured into crushed ice (250 mL) containing conc. ammonium hydroxide (100 mL). The resulting slurry was stirred with the addition of Et2O and filtered through celite. The filtrate was diluted with Et2O and partitioned. The aqueous portion was extracted with Et2O four times. The combined organic portions were washed with brine and dried (MgSO4). Filtration and concentration in vacuo followed by radial chromatography (SiO2, 0-60% EtOAc-hexanes gradient) afforded the title compound as a solid (9 g, 64%): 1H NMR (400 MHz, CDCl3) δ 8.45 (s, 1H), 7.50 (d, J=9.0 Hz, 1H), 7.47 (d, J=9.0 Hz, 1H), 6.54 (s, 1H), 2.52 (s, 3H); MS (ES) m/z 225 (M+1).

Provenance & Evidence