Cyclobutanone → 4-(4-(2-Cyanopropan-2-ylamino)-2-fluorophenyl)-N,N-dimethylbutanamide

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-(4-Amino-2-fluorophenyl)-N,N-dimethylbutanamide (76) (10 mg, 0.05 mmol), cyclobutanone (6 mg, 0.09 mmol) and trimethylsilyl cyanide (TMSCN, 9 mg, 0.09 mmol) was heated to 80° C. and stirred for 15 h. To the medium was added ethyl acetate (2×20 mL) and then washed with water (2×20 mL). The organic layer was dried over MgSO4 and concentrated and the residue was purified with silica gel column chromatography (dichloromethane:acetone, 9:1) to give 4-(4-(2-Cyanopropan-2-ylamino)-2-fluorophenyl)-N,N-dimethylbutanamide (75) (12 mg, 89%): 1H NMR δ 7.04 (dd, 1H, J=8.0, 7.8 Hz), 6.36 (dd, 1H, J=8.0, 2.3 Hz), 6.32 (dd, 1H, J=11.6, 2.3 Hz), 4.08 (br s, 1H), 2.96 (s, 3H), 2.93 (s, 3H), 2.77-2.81 (m, 2H), 2.61 (t, 2H, J=7.4 Hz) 2.35-2.38 (m, 2H), 2.31 (t, 2H, J=7.6 Hz), 2.10-2.37 (m, 2H), 1.87-1.95 (m, 2H).

Provenance & Evidence