反应详情

温度

100 °C

To a degassed solution of 4-(2,5-difluoro-4-aminophenoxy)-3-iodo-2-[bis[(1,1-dimethylethoxy)carbonyl]amino]pyridine (0.7 g, 1.24 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.52 g, 2.48 mmol) in dioxane (15 mL) was added K2CO3 (0.51 g, 3.7 mmol) in water (3 mL). Tetrakis (triphenylphosphine)Palladium(0) (0.14 g, 0.12 mmol) was added and the reaction mixture was stirred at 100° C. for 3 h. The mixture was diluted with water (40 mL) and EtOAc (50 mL). The layers were separated, and the aq. layer was extracted with EtOAc (20 mL). The combined organics were washed with brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by silica gel chromatography (EtOAc-hexanes) to afford 4-(4-amino-2,5-difluorophenoxy)-3-(1-methyl-1H-pyrazol-4-yl)-2-[bis[(1,1-dimethylethoxy)carbonyl]amino]pyridine as a colorless foam (0.52 g, 81% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.17 (d, J=5.6 Hz, 1H), 7.84 (s, 1H), 7.48 (d, J=0.8 Hz, 1H), 7.21 (dd, J=11.2 Hz, 7.6 Hz, 1H), 6.70 (m, 2H), 5.50 (s, 2H), 3.86 (s, 3H), 1.25 (s, 18H); MS (ESI) m/z: 518.3 (M+H+).

1. customThe layers were separated
2. extractionthe aq. layer was extracted with EtOAc (20 mL)
3. washThe combined organics were washed with brine
4. dry with materialdried (Na2SO4)
5. concentrationconcentrated in vacuo
6. customThe residue was purified by silica gel chromatography (EtOAc-hexanes)