反应详情

温度

50 °C

To a flask containing N-(3-fluoro-4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)biphenyl-3-carboxamide (10 mg, 0.015 mmol) at room temperature under a drying tube was added TFA (1 mL). The solution was warmed to 50° C. for 3 hours. After cooling to ambient temperature, the solution was concentrated, and the residue was redissolved in 5 mL dichloromethane and stirred rapidly with 5 mL 10% sodium carbonate solution to provide the free base. The organic layer was isolated, dried (MgSO4), filtered and concentrated. The crude product was passed through a small gravity silica cartridge with 95/5 dichloromethane/MeOH to provide the desired product as a clear oil (2.2 mg, 27% yield). 1H NMR (400 MHz, CDCl3) δ 9.40 (br s, 1H), 8.20 (d, 1H), 8.11 (m, 1H), 8.01 (m, 1H), 7.92 (m, 1H), 7.85 (m, 1H), 7.82 (m, 1H), 7.65 (m, 2H), 7.60 (m, 1H), 7.50 (m, 2H), 7.41 (m, 2H), 7.30 (m, 1H), 6.10 (d, 1H), 4.54 (m, 1H), 3.73 (br m, 1H), 2.89 (br m, 2H), 2.34 (s, 3H), 2.24 (br m, 3H), 1.68 (br m, 2H). LCMS (APCI+): m/z 537 (M+1) detected.

1. temperatureAfter cooling to ambient temperature
2. concentrationthe solution was concentrated
3. dissolutionthe residue was redissolved in 5 mL dichloromethane
4. customto provide the free base
5. customThe organic layer was isolated
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated