反应详情

温度

70 °C

A stirred mixture of N-(3-fluoro-4-(1-(4-methoxybenzyl)-3-(3-(methylcarbamoyl)phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (35 mg, 0.050 mmol) and TFA (0.5 mL) was heated to 70° C. for 3 hours, or until reaction was complete as determined by LC/MS. The mixture was concentrated in vacuo, using toluene (2×5 mL) to azeotrope residual TFA. The crude was purified by silica gel column chromatography (Biotage 12M) eluting with 1-10% MeOH/CHCl3 to give the desired product as off-white solid (19 mg, 55%). 1H NMR (400 MHz, DMSO-d6) δ 14.03 (s, 1H), 10.39 (s, 1H), 10.00 (s, 1H), 8.49 (s, 2H), 8.38 (d, 1H), 8.12 (d, 1H), 7.87 (m, 2H), 7.64 (m, 2H), 7.55 (t, 1H), 7.47 (m, 2H), 7.15 (t, 2H), 6.32 (d, 1H), 2.78 (d, 3H), 1.47 (d, 4H). LRMS (APCI pos) m/e 583.1 (M+H).

1. customuntil reaction
2. concentrationThe mixture was concentrated in vacuo
3. customThe crude was purified by silica gel column chromatography (Biotage 12M)
4. washeluting with 1-10% MeOH/CHCl3