Methylamine → 1-(4-(2,5-Difluoro-4-(1-(4-fluorophenyl)-4-(methylamino)-2-oxo-1,2-dihydropyridine-3-carboxamido)phenoxy)pyridin-2-yl)-3-methylurea

Participants

Reaction Steps

Prop-1-en-2-yl (4-(4-(4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamido)-2,5-difluorophenoxy)pyridin-2-yl)carbamate (0.14 g, 0.24 mmol) was treated with a solution of N-methylamine (2.0 M in THF, 4 mL, 8 mmol) and N-methylpyrrolidine (0.021 g, 0.24 mmol), and was stirred at RT for 3 h. The solid was collected by filtration and further purified by silica gel chromatography (EtOAc). The purified residue was treated with MeCN/H2O (1:1, 4 mL), frozen and lyophilized to obtain 1-(4-(2,5-difluoro-4-(1-(4-fluorophenyl)-4-(methylamino)-2-oxo-1,2-dihydropyridine-3-carboxamido)phenoxy)pyridin-2-yl)-3-methylurea (23 mg, 18% yield) as an off-white powder. 1H NMR (400 MHz, DMSO-d6): δ 13.21 (s, 1 H), 10.35 (d, J=6.0 Hz, 1 H), 9.13 (s, 1 H), 8.48 (dd, J=12.9, 7.2 Hz, 1 H), 8.06 (d, J=5.9 Hz, 1 H), 7.83 (s, 1 H), 7.72 (d, J=7.8 Hz, 1 H), 7.48 (m, 3 H), 7.34 (t, J=8.5 Hz, 2 H), 6.92 (s, 1 H), 6.57 (dd, J=6.0, 2.4 Hz, 1 H), 6.24 (d, J=7.9 Hz, 1 H), 3.01 (d, J=5.0 Hz, 3 H), 2.66 (d, J=4.6 Hz, 3 H); MS (ESI) m/z: 539.2 (M+H+).

Provenance & Evidence