Water → Bms-777607

Participants

Reaction Steps

To a mixture of 3-chloro-4-(4-(4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamido)-2-fluorophenoxy)picolinamide (13.9 g, 25.7 mmol) in EtOAc (200 mL), MeCN (200 mL), and water (100 mL) at 0° C. was added iodobenzene diacetate (9.93 g, 30.8 mmol). The reaction mixture was slowly warmed to room temperature and stirred for 1 h. The resulting precipitate was filtered and washed with ethyl acetate. The combined filtrates were washed with saturated aqueous sodium bicarbonate solution and the organic phase was dried over anhydrous sodium sulfate and concentrated in vacuo. This residue and the original precipitate were combined and purified by flash chromatography (SiO2, 0-2% methanol/chloroform gradient elution) to give N-(4-(2-Amino-3-chloropyridin-4-yloxy )-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (9.8 g, 74%) as an off-white solid. 1H NMR (DMSO-d6) δ 10.57 (s, 1H), 7.83-7.79 (m, 2H), 7.67 (d, 1H, J=5.6 Hz), 7.41-7.38 (m, 3H), 7.36-7.22 (m, 3H), 6.44 (d, 1H, J=7.6 Hz), 6.36 (br s, 2H), 5.86 (d, 1H, J=6.0 Hz), 4.18 (q, 2H, J =7.2 Hz), 1.23 (t, 3H, J=7.2 Hz); MS (ESI+) m/z 513.09 (M+H)+.

Provenance & Evidence