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 (76.3 mg, 0.172 mmol) was dissolved in DCM (2.9 mL) and trifluoroacetic acid (Aldrich, St. Louis, Mo., hplc grade, 0.60 mL, 7.8 mmol) was added via syringe. The reaction was stirred at room temperature for 35 minutes, concentrated, treated with MeOH, and filtered. The solid was washed with Et2O, but was not sufficiently (>95% by HPLC) pure. So, the solid and filtrate were combined, concentrated, treated with 2N ammonia in MeOH, and concentrated again. The material was treated with Et2O, but this did not precipitate product. So, it was concentrated, treated with water, and filtered. The solid was washed with water, but was still not 95% pure. So, the solid was collected and purified on HPLC (10% to 100% MeCN/water over 30 minutes using a total flow rate of 100 mL/min) to afford N-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)-5-vinylpyridin-2-amine (68.6 mg). MS (ESI pos. ion) m/z 360 (M+H)+. 1H NMR (d6-DMSO) δ 12.70 (s, 1H), 9.98 (s, 1H), 8.65 (s, 1H), 8.55 (d, J=2.54 Hz, 1H), 8.40 (d, J=2.35 Hz, 1H), 8.19 (dd, J=8.8 Hz, 2.74 Hz, 1H), 6.86 (d, J=8.8 Hz, 1H), 6.79 (dd, J=17.5 Hz, 10.9 Hz, 1H), 5.78 (d, J=16.4 Hz, 1H), 5.26 (d, J=11.0 Hz, 1H), 3.85 (s, 3H), 2.86 (s, 3H).

1. concentrationconcentrated
2. additiontreated with MeOH
3. filtrationfiltered
4. washThe solid was washed with Et2O
5. concentrationconcentrated
6. additiontreated with 2N ammonia in MeOH
7. concentrationconcentrated again
8. additionThe material was treated with Et2O
9. customthis did not precipitate product
10. concentrationSo, it was concentrated
11. additiontreated with water
12. filtrationfiltered
13. washThe solid was washed with water
14. customSo, the solid was collected
15. custompurified on HPLC (10% to 100% MeCN/water over 30 minutes