反应详情

温度

60 °C

To a solution of N-cyclobutyl-2-(4-(2,4-difluorophenoxyl)piperidin-1-yl)pyrido[3,4-b]pyrazin-3-amine (12.0 g, 29.2 mmol) in acetone (200 mL) and dioxane (300 mL) was added Ac2O (30 mL, 318 mmol) and Pd/C (1.80 g, 16.91 mmol). The reaction was then stirred at 60° C. under H2 atmosphere (345 kPa) for 72 h. Then the mixture was filtered through a pad of Celite™, washing with EtOAc. The reaction solution was diluted with EtOAc (50 mL) and poured into saturated aqueous NaHCO3 (50 mL), then washed with brine (2×30 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude product was recrystallized with PEEtOAc, lyophilized and washed with PEEtOAc (5:1) to give pure title compound (6.1 g). 1H NMR (500 MHz, DMSO-d6, mixture of rotamers) δ ppm 1.57-1.74 (m, 2H), 1.85-1.95 (m, 2H), 1.97-2.08 (m, 4H), 2.08 (s, 1.3H), 2.09 (s, 1.7H), 2.19-2.30 (m, 2H), 2.58 (t, J=5.9 Hz, 0.9H), 2.71 (t, J=5.9 Hz, 1.1H), 2.88 (t, J=10.5 Hz, 2H), 3.23-3.33 (m, 2H), 3.70 (dt, J=11.7, 5.9 Hz, 2H), 4.32-4.47 (m, 3H), 4.52 (tt, J=8.1, 3.8 Hz, 1H), 6.05 (d, J=7.8 Hz, 0.4H), 6.08 (d, J=8.3 Hz, 0.6H 6.96-7.07 (m, 1H), 7.24-7.36 (m, 2H); ESI-MS m/z [M+H]+ 458.00.

1. filtrationThen the mixture was filtered through a pad of Celite™
2. washwashing with EtOAc
3. additionThe reaction solution was diluted with EtOAc (50 mL)
4. additionpoured into saturated aqueous NaHCO3 (50 mL)
5. washwashed with brine (2×30 mL)
6. dry with materialThe organic layer was dried over Na2SO4
7. concentrationconcentrated in vacuo
8. customThe crude product was recrystallized with PEEtOAc
9. washwashed with PEEtOAc (5:1)