反应详情

温度

50 °C

To a flask containing N-(4-(1-(4-methoxybenzyl)-3-(4-(dimethylamino)piperidin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-1-(benzo[d]oxazol-2-yl)cyclopropanecarboxamide (6.6 mg, 0.01 mmol) at room temperature under a drying tube was added TFA (2 mL). The reaction was warmed to 50° C. overnight. The reaction was cooled to room temperature and was concentrated. The residue was dissolved in 10 mL dichloromethane and stirred rapidly with 10 mL 10% sodium carbonate solution. The layers were separated and the organics dried (MgSO4). The crude product was concentrated and the crude material was loaded onto a Biotage 12S column with dichloromethane. The column was eluted with a step gradient of dichloromethane (150 mL) and 94.5/5/0.5 dichloromethane/MeOH, concentrated ammonium hydroxide to provide the desires product as a yellow glass (2.7 mg, 50% yield). 1H NMR (400 MHz, CDCl3) δ 12.17 (br s, 1H), 9.92 (br s, 1H), 8.24 (d, 1H), 7.90 (m, 1H), 7.73 (m, 1H), 7.48 (m, 2H), 7.38 (m, 2H), 7.30 (m, 1H), 6.21 (d, 1H), 4.11 (m, 2H), 2.91 (m, 2H), 2.40 (m, 1H), 2.34 (s, 6H), 2.08 (m, 2H), 1.96 (br m, 2H), 1.90 (m, 2H), 1.74 (br m, 2H). LCMS (APCI+): m/z 556 (M+1) detected.

1. temperatureThe reaction was cooled to room temperature
2. concentrationwas concentrated
3. dissolutionThe residue was dissolved in 10 mL dichloromethane
4. customThe layers were separated
5. dry with materialthe organics dried (MgSO4)
6. concentrationThe crude product was concentrated
7. washThe column was eluted with a step gradient of dichloromethane (150 mL) and 94.5/5/0.5 dichloromethane/MeOH, concentrated ammonium hydroxide