反应详情

N-(6-Methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-vinylpyridin-2-amine (62.0 mg, 0.140 mmol) and palladium on activated carbon (Aldrich, St. Louis, Mo. 10% Pd, 19.1 mg) were added to MeOH (2.0 mL) and TFA (0.30 mL). The reaction flask was evacuated and back-filled with hydrogen, and the reaction was stirred at room temperature for one hour. Then, the hydrogen balloon was removed, and stirring was continued at room temperature, without the balloon of hydrogen, for 90 minutes. Then, the reaction flask was fitted with a reflux condenser and put in a preheated oil bath (45° C.-50° C.), and stirring was continued under nitrogen overnight. The reaction was cooled to room temperature and filtered through a pad of Celite® (diatomaceous earth), which was washed with DCM and MeOH and a couple of drops of TFA. The filtrate was concentrated and purified on HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 mL/min). The fractions with product were collected, concentrated, and dried under high vacuum in a water bath (50° C.). Then, the material was washed with Et2O, MeOH, and Et2O, collected, and dried under high vacuum overnight to give 5-ethyl-N-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)pyridin-2-amine (17.8 mg, 35% yield). MS (ESI pos. ion) m/z 362 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 12.53 (s, 1H), 9.72 (s, 1H), 8.62 (s, 1H), 8.53 (d, J=2.54 Hz, 1H), 8.22-8.13 (m, 2H), 6.84 (d, J=8.8 Hz, 1H), 3.84 (s, 3H), 2.85 (s, 3H), 2.65 (q, J=7.37 Hz, 2H), 1.26 (t, J=7.53 Hz, 3H).

1. customThe reaction flask was evacuated
2. additionback-filled with hydrogen
3. customThen, the hydrogen balloon was removed
4. stirringstirring
5. waitwas continued at room temperature, without the balloon of hydrogen, for 90 minutes
6. customThen, the reaction flask was fitted with a reflux condenser
7. customput in a preheated oil bath
8. stirring(45° C.-50° C.), and stirring
9. waitwas continued under nitrogen overnight
10. temperatureThe reaction was cooled to room temperature
11. filtrationfiltered through a pad of Celite® (diatomaceous earth), which
12. washwas washed with DCM and MeOH and a couple of drops of TFA
13. concentrationThe filtrate was concentrated
14. custompurified on HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 mL/min)
15. customThe fractions with product were collected
16. concentrationconcentrated
17. customdried under high vacuum in a water bath (50° C.)
18. washThen, the material was washed with Et2O, MeOH, and Et2O
19. customcollected
20. customdried under high vacuum overnight