反应详情

温度

80 °C

A mixture of 2-(4-chloro-7-fluoropyrazolo[4,3-c]pyridin-2-yl)-5-fluorobenzonitrile (185 mg, 0.5 mmol), 2-(6-amino-2-methylpyrimidin-4-ylamino)ethanol (101 mg, 0.6 mmol), Pd2(dba)3 (11 mg, 0.0125 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. The reaction mixture was heated at 80° C. in a sealed vial overnight. After cooling, the resultant mixture was diluted with ethyl acetate and washed with water. 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 (0-2% methanol in ethyl acetate) to afford crude product. This was dissolved in 1.25 N HCl in propan-2-ol solution (10 mL) and was stirred at room temperature for 1 hour. The solvent was concentrated under reduced pressure, and diethyl ether was added and the mixture was stirred for 5 minutes. The precipitate was filtered off and dried to afford the title compound as an off-white solid (68 mg, 28% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.52 (br s, 1H), 8.35-8.29 (m, 2H), 8.07 (s, 1H), 7.13 (br s, 1H), 3.66-3.59 (m, 2H), 3.59-3.49 (m, 2H), 2.59 (s, 3H). LCMS (Method B): RT=3.13 min, m/z: 457 [M+H+].

1. customwas de-gassed
2. custompurged with nitrogen
3. temperatureAfter cooling
4. additionthe resultant mixture was diluted with ethyl acetate
5. washwashed with water
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 (0-2% methanol in ethyl acetate)
11. customto afford crude product
12. concentrationThe solvent was concentrated under reduced pressure, and diethyl ether
13. additionwas added
14. stirringthe mixture was stirred for 5 minutes
15. filtrationThe precipitate was filtered off
16. customdried