Anisole → N1-(4-(2-Aminopyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamide

Participants

Reaction Conditions

Reaction Steps

A mixture of N1-(4-(2-(4-methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamide (Example 14, 25 mg, 0.048 mmol), anisole (52 mg, 0.48 mmol) in TFA (1 mL) was heated at 85° C. for 6 h. The TFA was removed under vacuum and the residue partitioned between EtOAc and saturated aq. NaHCO3 solution. The EtOAc phase was washed with brine, dried (MgSO4), and concentrated in vacuo. Flash chromatography on SiO2 using EtOAc then 1-2% MeOH in CH2Cl2 as eluents gave the title compound (12 mg, 63%) as an off-white solid. 1H NMR (DMSO-d6) δ 11.00 (s, 1H), 10.51 (s, 1H), 8.02 (s, 1H), 7.66 (dd, 1H, J=12.6, 2.0 Hz), 7.42-7.31 (m, 2H), 7.32-7.27 (m, 1H), 7.23 (t, 2H, J=8.6 Hz), 7.16 (t, 2H, J=9.1 Hz), 6.91 (s, 2H), 3.73 (s, 2H); MS(ESI+) m/z 400.11 (M+H)+.

Provenance & Evidence