反应详情

温度

60 °C

To a solution of (S)-2-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-N-(tetrahydrofuran-3-yl)pyrido[3,4-b]pyrazin-3-amine (2.0 g, 4.68 mmol) in dioxane:acetone (50 ml; 1.5:1) was added Ac2O (4.8 mL, 50.9 mmol) and Pd/C (400 mg, 3.76 mmol); then, the reaction was stirred at 60° C. under H2 atmosphere (345 kPa) for 72 h. The mixture was filtered through a pad of Celite™ and washed with EtOAc. The reaction solution was diluted with EtOAc (50 mL) and poured into sat. aqueous NaHCO3 (50 ml), then washed with brine (2×30 mL). The organic layer was dried over Na2SO4 and concentrated to give the crude product, which was purified by flash column chromatography to yield the title compound (193.4 mg) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.88-1.89 (m, 4H), 2.05-2.09 (m, 4H), 2.60-2.90 (m, 4H), 3.30-3.40 (m, 4H), 3.55-3.57 (m, 1H), 3.68-3.74 (m, 2H), 3.85-3.95 (m, 2H), 4.38-4.51 (m, 4H), 5.91 (dd, J=6.0, 4.4 Hz, 1H), 7.01 (m, 1H), 7.25-7.31 (m, 2H); ESI-MS m/z [M+H]+ 474.3.

1. filtrationThe mixture was filtered through a pad of Celite™
2. washwashed with EtOAc
3. additionThe reaction solution was diluted with EtOAc (50 mL)
4. additionpoured into sat. aqueous NaHCO3 (50 ml)
5. washwashed with brine (2×30 mL)
6. dry with materialThe organic layer was dried over Na2SO4
7. concentrationconcentrated
8. customto give the crude product, which
9. customwas purified by flash column chromatography