反应详情

温度

70 °C

Nitrogen was bubbled though a solution of 4-(2-chloro-pyridin-4-yloxy)-2,3-difluoro-phenylamine (2 g, 7.8 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (1.6 g, 7.8 mmol) and Na2CO3 (1.65 g, 15.6 mmol) in DME (12 mL) and H2O (4 mL) for 20 min. Pd(PPh3)4 (450 mg, 0.4 mmol), was added and then resulting mixture was degassed in vacuo, blanketed with nitrogen and heated to 70° C. for 16 h. The reaction was concentrated to dryness under reduced pressure. The crude product was suspended in water and extracted with EtOAc (3×10 mL). The organic layer was washed with brine, dried (Na2SO4), concentrated in vacuo and purified by silica gel chromatography to give 2,3-difluoro-4-[2-(1-methyl-1H-pyrazol-4-yl)-pyridin-4-yloxy]-phenylamine (1.3 g, 55% yield). 1H NMR (400 MHz, DMSO-d6), δ 8.40 (d, J=6.0 Hz, 1 H), 8.32 (s, 1 H), 8.02 (s, 1 H), 7.26 (s, 1 H), 6.96 (t, J=8.8 Hz, 1 H), 6.71-6.68 (m, 2 H), 5.62 (s, 2 H), 3.92 (s, 3 H); MS (ESI) m/z: 303.2[M+H]+.

1. customresulting mixture
2. customwas degassed in vacuo
3. concentrationThe reaction was concentrated to dryness under reduced pressure
4. extractionextracted with EtOAc (3×10 mL)
5. washThe organic layer was washed with brine
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated in vacuo
8. custompurified by silica gel chromatography