Tetrahydrofuran → 2-[2-[3-Methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-6-(4 fluoromethyl-phenyl)-pyrimidin-4-yl]-propan-2-ol

Participants

Reaction Conditions

Reaction Steps

To a solution of ethyl 2-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-6-(4-trifluoromethyl-phenyl)-pyrimidine-4-carboxylate (597 mg, 1.2 mmol) in tetrahydro-furane (25 mL) was added at 0° C. over 2 min a 3 M solution of methylmagnesiumchloride in tetrahydrofurane (1.68 mL, 5.04 mmol). The reaction mixture was stirred at 0° C. for 15 min followed by 1.5 h at 20° C. The mixture was poured on saturated sodium carbonate solution (20 mL) and the product was extracted with ethyl acetate (80 mL). The organic layer was washed with brine (20 mL), dried over sodium sulfate and evaporated under reduced pressure. The residual material was purified by chromatography on silica gel using dichloromethane/0-10% methanol as eluent. Following a more liopophilic by-product (54 mg, example 175) the title compound was eluted and crystallized from dichloromethane/diethyl ether to give a white solid (314 mg, 54%). MS ISP (m/e): 484.4 [(M+H)+]. 1H NMR (CDCl3, 300 MHz): δ (ppm)=8.21 (d, 2H), 7.82 (d, 1H), 7.77 (d, 2H), 7.66 (s, 1H), 7.36 (s, 2H), 7.22 (d, 1H), 7.10 (dd, 1H), 6.90 (s, 1H), 3.90 (s, 3H), 3.84 (br s, 1H), 2.31 (s, 3H), 1.56 (s, 6H).

Provenance & Evidence