反应详情

The crude 2-(6-(6-methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)ethanol (193 mg, 0.418 mmol) was dissolved in MeOH (5.0 mL) and TFA (0.50 mL, 6.49 mmol) was added via syringe. The reaction was stirred at room temperature for 2.5 hours, and then more TFA (0.9 mL) was added, and stirring was continued overnight. Then, the flask was fitted with a reflux condenser and placed in a preheated oil bath (60° C.), stirring was continued for 75 minutes. (This 75 minute period was interrupted by an approximate 15 minute period where the flask was not in the oil bath.) The reaction was cooled to room temperature and filtered through a Celite® (diatomaceous earth) pad, which was washed with DCM and MeOH. The filtrate was concentrated and purified by prep HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 mL/min) to give 2-(6-(6-methoxypyridin-3-ylamino)-5-(2-methyl-9H-purin-6-yl)pyridin-3-yl)ethanol (56.0 mg, 35% yield over 2 steps). MS (ESI pos. ion) m/z 378 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 12.50 (s, 1H), 9.66 (s, 1H), 8.62 (s, 1H), 8.53 (s, 1H), 8.20-8.14 (m, 2H), 6.86 (d, J=8.8 Hz, 1H), 3.85 (s, 3H), 3.66 (t, J=6.86 Hz, 2H), 2.85 (s, 3H), 2.76 (t, J=6.86 Hz, 2H).

1. stirringstirring
2. waitwas continued overnight
3. customThen, the flask was fitted with a reflux condenser
4. customplaced in a preheated oil bath
5. stirring(60° C.), stirring
6. waitwas continued for 75 minutes
7. wait(This 75 minute period was interrupted by an approximate 15 minute period
8. temperature) The reaction was cooled to room temperature
9. filtrationfiltered through a Celite® (diatomaceous earth) pad, which
10. washwas washed with DCM and MeOH
11. concentrationThe filtrate was concentrated
12. custompurified by prep HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 mL/min)