反应详情

A mixture of 1-(4-chloro-5-(1-ethyl-7-((4-methoxybenzyl)(methyl)amino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-(2,5-difluorophenyl)urea (314 mg, 0.505 mmol) and anisole (273 mg, 2.52 mmol) was treated with TFA (3.0 mL, 51.9 mmol) and stirred at RT for 2.5 h. The mixture was concentrated to near-dryness, treated with EtOAc and satd. NaHCO3 and the resulting solid collected via filtration and dried to afford 1-(4-chloro-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-(2,5-difluorophenyl)urea (233 mg, 92% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.24 (m, 2H), 8.40 (s, 1H), 8.17 (d, J=8.7 Hz, 1H), 7.97 (m, 1H), 7.73 (s, 1H), 7.54 (d, J=11.0 Hz, 1H), 7.27 (m, 1H), 7.02 (m, 1H), 6.80 (m, 1H), 6.23 (s, 1H), 4.12 (q, J=7.1 Hz, 2H), 2.85 (d, J=4.9 Hz, 3H), 1.19 (t, J=7.0 Hz, 3H); MS (ESI) m/z: 502.2 [M+H]+.

1. concentrationThe mixture was concentrated to near-dryness
2. additiontreated with EtOAc and satd
3. filtrationNaHCO3 and the resulting solid collected via filtration
4. customdried