Dimethylformamide → HCID 15952818, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-chloro-N-({1-(cyclopropylmethyl)-4-[(cyclopropylmethyl)sulfonyl]cyclohexyl}methyl)-2-(trifluoromethyl)nicotinamide (37 mg, 0.076 m-mol), zinc cyanide (44 mg, 0.38 mmol) and tetrakis triphenylphosphine palladium (0) (8.7 mg, 0.008 mmol) in N,N-dimethylformamide (1.5 mL) was heated at 150° C. for 600 s under microwave irradiation. The mixture was allowed to cool to ambient temperature, the supernatant layer removed and evaporated. The residue was partitioned between dichloromethane (5 ml) and water (5 ml) and stirred vigorously for 5 min. The mixture separated using a 5 micron PTFE frit and the filtrate was evaporated. The yellow oil was purified by preparative plate chromatography eluting with 10% ethyl acetate in dichloromethane. Collecting the appropriate band followed by trituration with ethyl acetate, filtration of the solid and evaporation of the filtrate gave a white solid. The solid was recrystallised from ethyl acetate/isohexane which gave 6-cyano-N-({1-(cyclopropylmethyl)-4-[(cyclopropylmethyl)sulfonyl]cyclohexyl}methyl)-2-(trifluoromethyl)-nicotinamide a white solid (21 mg, 57%): 1H NMR (400 MHz, CDCl3) δ 8.11 (1H, d, J=7.9 Hz), 7.95 (1H, d, J=7.9 Hz), 5.98 (1H, s), 3.61 (2H, d, J=6.3 Hz), 2.98-2.88 (3H, m), 2.04-2.01 (2H, m), 1.96-1.84 (4H, m), 1.43-1.37 (2H, m), 1.24 (2H, d, J=6.7 Hz), 1.18-1.12 (1H, m), 0.76 (2H, q, J=6.4 Hz), 0.68-0.64 (1H, m), 0.53-0.49 (2H, m), 0.41 (2H, q, J=5.3 Hz), 0.06-0.05 (2H, m); m/z=484 (M+H+).

Provenance & Evidence