反应详情

温度

150 °C

A mixture of 4-bromo-2-(2,6-dichlorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine (320 mg, 0.89 mmol), N-(6-aminopyrimidin-4-yl)-acetamide (152 mg, 1.0 mmol), Pd2(dba)3 (20 mg, 0.022 mmol), Xantphos (52 mg, 0.089 mmol) and cesium carbonate (580 mg, 1.78 mmol) in dioxane (10 mL) was de-gassed and purged with nitrogen and the reaction mixture was heated at 150° C. in the microwave for 1 h. The resultant mixture was partitioned between ethyl acetate and water and the layers were separated. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (80-100% ethyl acetate in cyclohexane) to afford an off-white solid. This was re-purified by HPLC [gradient: 5 to 98% acetonitrile (0.1% ammonium hydroxide) in water (0.1% ammonium hydroxide)], to afford the title compound as a white solid (31 mg, 10% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.65-10.61 (m, 2H), 9.26 (d, J=2.6 Hz, 1H), 9.08 (d, J=1.1 Hz, 1H), 8.53 (d, J=1.1 Hz, 1H), 7.92 (d, J=3.4 Hz, 1H), 7.83-7.81 (m, 2H), 7.74 (dd, J=9.1, 7.3 Hz, 1H), 2.14 (s, 3H). LCMS (Method B): RT=3.20 min, m/z: 432 [M+H+].

1. customwas de-gassed
2. custompurged with nitrogen
3. customThe resultant mixture was partitioned between ethyl acetate and water
4. customthe layers were separated
5. washThe organic layer was washed with brine
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by silica gel flash chromatography (80-100% ethyl acetate in cyclohexane)
10. customto afford an off-white solid
11. customThis was re-purified by HPLC [gradient: 5 to 98% acetonitrile (0.1% ammonium hydroxide) in water (0.1% ammonium hydroxide)]