Imidazole → N-[5-(1H-imidazol-1-yl)-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide

Participants

Reaction Conditions

Reaction Steps

A mixture of N-(5-bromo-2-methylphenyl)-4-[(4-phenylquinazolin-2-yl)amino]benzamide (198 mg, 0.39 mmol), prepared as described in Example 14, copper (I) iodide (90 mg, 0.47 mmol), 1S,2S—N1,N2-dimethylcyclohexane-1,2-diamine (25 mg, 0.17 mmol), cesium carbonate (270 mg, 0.83 mmol) and imidazole (40 mg, 0.59 mmol) in dimethylformamide (400 μL) were combined in a sealed tube under an atmosphere of nitrogen and heated to 110° C. overnight. Upon cooling to rt, the reaction mixture was partitioned between saturated sodium bicarbonate and ethyl acetate. Insoluble material was filtered and the two layers of filtrate were separated. The aqueous phase was further extracted with ethyl acetate, and the combined organic layers were washed with saturated sodium chloride, dried over sodium sulfate and concentrated on a rotary evaporator. The resulting residue was purified by preparative reverse phase HPLC to give N-[5-(1H-imidazol-1-yl)-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide (31 mg, 16%). 1H NMR (400 MHz, DMSO-d6): δ 10.37 (s, 1H), 9.88 (s, 1H), 8.26 (s, 1H), 8.20 (d, 2H), 8.02 (d, 2H), 7.90-7.70 (m, 8H), 7.65 (m, 2H), 7.45 (m, 3H), 7.12 (s, 1H), 2.30 (s, 3H). MS (EI) for C31H24N6O: 497.2 (MH+).

Provenance & Evidence