反应详情

温度

80 °C

To a solution of 6-bromo-1-cyclopropyl-2-(5-trifluoromethyl-pyridin-3-yl)-1H-benzoimidazole (0.15 g, 0.00026 mol) in ethanol toluene water (6 ml 3 ml 1.5 ml respectively) mixture in a sealed tube was added 3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.1 g, 0.00052 mol) and Na2CO3 (0.082 g, 0.000785 mol) and argon was purged for 15 min. Then Pd (PPh3)4 (0.015 g, 0.000013 mol) was added and heated at 80° C. for 5 h. The solvent was evaporated and the resulting residue was added water. The aqueous layer was extracted with ethyl acetate (3×20 ml). The combined organic layers were washed with brine dried over Na2SO4 and concentrated under vacuum to afford the crude compound which was purified by column chromatography to obtain title compound 1-cyclopropyl-6-(1H-pyrazol-3-yl)-2-[5-(trifluoromethyl)pyridin-3-yl]-1H-benzimidazole (321) as an off white solid. NMR (400 MHz, DMSO-d6), δ: 12.85 (s, 1H), 9.49 (s, 1H), 9.12 (s, 1H), 8.75 (s, 1H), 8.09 (s, 1H), 7.79-7.67 (m, 3H), 7.54-7.52 (m, 1H), 6.79 (s, 1H), 3.96 (bs, 1H), 1.15 (d, J=5.6 Hz, 2H), 0.73 (bs, 2H). MS (M+1): 370.6, Purity 99.94%.

1. customwas purged for 15 min
2. customThe solvent was evaporated
3. additionthe resulting residue was added water
4. extractionThe aqueous layer was extracted with ethyl acetate (3×20 ml)
5. washThe combined organic layers were washed with brine
6. dry with materialdried over Na2SO4
7. concentrationconcentrated under vacuum
8. customto afford the crude compound which
9. customwas purified by column chromatography