反应详情

温度

100 °C

3-Methyl-5-(1,3-thiazol-5-yl)aniline (0.250 g, 1.31 mmol), the product of Step 1 (0.227 g, 1.31 mmol), palladium(II) acetate (0.0295 g, 0.131 mmol), xantphos (0.114 g, 0.197 mmol), and cesium carbonate (0.856 g, 2.63 mmol) were added to a dry flask. The flask was degassed with argon and then dioxane (4.4 ml) was added. The reaction mixture was degassed with argon for 5 minutes, and then heated to 100° C. After 2 hours, the reaction mixture was cooled to room temperature, diluted with ethyl acetate, washed with brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by flash chromatography on silica gel (EtOAc/dichloromethane gradient) to afford 4-cyclopropyl-5-fluoro-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amine (0.390 g, 1.20 mmol, 91% yield). MS ESI: [M+H]+ m/z 326.8. 1H NMR (500 MHz, DMSO-d6) δ 9.59 (s, 1H); 9.06 (s, 1H); 8.38 (d, J=2.5 Hz, 1H); 8.19 (s, 1H); 7.94 (s, 1H); 7.39 (s, 1H); 7.10 (s, 1H); 2.29 (s, 31-1); 2.28-2.23 (m, 1H); 1.18-1.14 (m, 4H).

1. customThe flask was degassed with argon
2. additiondioxane (4.4 ml) was added
3. customThe reaction mixture was degassed with argon for 5 minutes
4. temperaturethe reaction mixture was cooled to room temperature
5. additiondiluted with ethyl acetate
6. washwashed with brine
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was purified by flash chromatography on silica gel (EtOAc/dichloromethane gradient)