反应详情

温度

100 °C

To a solution of 3-bromo-7-(2-chloro-3-(trifluoromethyl)benzyl)-6,7-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-8(5H)-one (100 mg, 0.24 mmol) and 4-fluorophenylboronic acid (40 mg, 0.27 mmol) in dioxane (0.6 mL) was added 1M Na2CO3 (0.6 mL). The flask was purged with nitrogen for 10 minutes and Pd(PPh3)4 (14 mg, 0.012 mmol) was added at once. The flask was purged with nitrogen for an additional 5 minutes and then heated at 100° C. for 18 h. After cooling to rt, brine was added, and the mixture was extracted with EtOAc (×3). The combined organic extracts were dried (Na2SO4), filtered, and concentrated to give a brown solid. Purification by chromatography (SiO2; hexanes—100% EtOAc) afforded the desired product as a white solid (47 mg, 45%). MS (ESI): mass calcd. for C19H13ClF4N4O, 424.1; m/z found, 425.1 [M+H]+. 1H NMR (500 MHz, DMSO-d6) δ 7.91-7.73 (m, 4H), 7.59-7.54 (m, 1H), 7.49-7.43 (m, 2H), 4.89 (s, 2H), 4.56-4.42 (m, 2H), 3.92-3.84 (m, 2H).

1. customThe flask was purged with nitrogen for 10 minutes
2. customThe flask was purged with nitrogen for an additional 5 minutes
3. temperatureAfter cooling to rt
4. additionbrine was added
5. extractionthe mixture was extracted with EtOAc (×3)
6. dry with materialThe combined organic extracts were dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customto give a brown solid
10. customPurification by chromatography (SiO2; hexanes—100% EtOAc)