反应详情

温度

90 °C

In a sealed tube, 4-(3-bromopyridin-4-yloxy)-2,5-difluorobenzenamine (0.42 g, 1.395 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.363 g, 1.744 mmol), potassium carbonate (0.578 g, 4.18 mmol), and tetrakistriphenylphosphine palladium (0) (0.081 g, 0.070 mmol) were suspended in dioxane (8 mL) and water (1.333 mL). The mixture was degassed with Ar and heated at 90° C. overnight. The reaction mixture was cooled and partitioned between EtOAc and saturated aqueous NaHCO3. The mixture was extracted with EtOAc (3×). The combined organic extracts were dried, evaporated and purified by silica gel chromatography (hexanes/EtOAc) to yield 2,5-difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamine (272 mg, 65% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.80 (s, 1H) 8.22-8.20 (m, 2H), 8.00 (s, 1H), 7.24-7.19 (tri, 1H), 6.76-6.71 (m, 1H), 6.62 (d, 1H), 5.50 (br s, 2H), 3.78 (s, 3H); MS (ESI) m/z: 301.0 (M+H+).

1. customThe mixture was degassed with Ar
2. temperatureThe reaction mixture was cooled
3. custompartitioned between EtOAc and saturated aqueous NaHCO3
4. extractionThe mixture was extracted with EtOAc (3×)
5. customThe combined organic extracts were dried
6. customevaporated
7. custompurified by silica gel chromatography (hexanes/EtOAc)