反应详情

温度

150 °C

A mixture of 4-bromo-2-(2-chloro-6-fluorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine (100 mg, 0.29 mmol), (4-amino-6-methylpyrimidin-2-yl)-methanol (42 mg, 0.31 mmol), Pd2(dba)3 (13 mg, 0.015 mmol), Xantphos (17 mg, 0.03 mmol) and cesium carbonate (189 mg, 0.58 mmol) in dioxane (2.0 mL) was de-gassed and purged with nitrogen and the reaction mixture was heated under microwave irradiation at 150° C. for 45 minutes. The resultant mixture was allowed to cool to room temperature and was then filtered through a pad of Celite® washing with further dioxane and then ethyl acetate. The combined washings were concentrated under reduced pressure and the resultant residue was purified by silica gel flash chromatography (40-100% ethyl acetate in cyclohexane). The resultant residue was further purified by HPLC (gradient: 10 to 98% MeOH (0.1% NH4OH) in water (0.1% NH4OH)], to afford the free base of the title compound. To this crude residue was added a solution of HCl (1.25 N in propan-2-ol, 2.0 mL) and the resulting mixture was stirred at room temperature for 1 hour. The resultant mixture was concentrated under reduced pressure and dried in vacuo to afford the title compound as a white solid (42 mg, 33% yield). 1H NMR (400 MHz, DMSO-d6): δ 12.24 (br s, 1H), 9.45 (s, 1H), 8.14 (d, J=3.3 Hz, 1H), 8.12 (br s, 1H), 7.83-7.75 (m, 1H), 7.74-7.63 (m, 2H), 4.71 (s, 2H), 2.63 (s, 3H). LCMS (Method B): RT=3.03 min, m/z: 403 [M+H+].

1. customwas de-gassed
2. custompurged with nitrogen
3. temperatureto cool to room temperature
4. filtrationwas then filtered through a pad of Celite®
5. washwashing with further dioxane
6. concentrationThe combined washings were concentrated under reduced pressure
7. customthe resultant residue was purified by silica gel flash chromatography (40-100% ethyl acetate in cyclohexane)
8. customThe resultant residue was further purified by HPLC (gradient