反应详情

温度

80 °C

A mixture of 4-bromo-2-(2-chloro-6-fluorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine (172 mg, 0.5 mmol), 4-amino-2,6-dimethylpyrimidine (74 mg, 0.6 mmol), Pd2(dba)3 (11 mg, 0.013 mmol), Xantphos (29 mg, 0.05 mmol) and cesium carbonate (326 mg, 1.0 mmol) in dioxane (5 mL) was de-gassed and purged with nitrogen and the reaction mixture was heated at 80° C. in a sealed vial overnight. The resultant mixture was allowed to cool to room temperature, before being partitioned between ethyl acetate and water. The layers were separated and 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 (ethyl acetate). The resultant residue was stirred with HCl (1.25 N in propan-2-ol, 5.0 mL) for 1 hour. The solid obtained was collected by filtration and dried to afford the title compound as an off-white solid (142 mg, 67% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.36 (s, 1H), 8.15 (br s, 1H), 8.11 (d, J=3.4 Hz, 1H), 7.81-7.73 (m, 1H), 7.73-7.62 (m, 2H), 2.65 (s, 3H), 2.59 (s, 3H). LCMS (Method B): RT=3.14 min, m/z: 387 [M+H+].

1. customwas de-gassed
2. custompurged with nitrogen
3. temperatureto cool to room temperature
4. custombefore being partitioned between ethyl acetate and water
5. customThe layers were separated
6. washthe organic layer was washed with brine
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by silica gel flash chromatography (ethyl acetate)
11. customThe solid obtained
12. filtrationwas collected by filtration
13. customdried