反应详情

温度

90 °C

To a solution of 4-(2-chloropyridin-4-yloxy)-2,5-difluoroaniline (450 mg, 1.76 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (400 mg, 1.9 mmol) in N,N-dimethylformamide (30 mL) was added tetrakis(triphenylphosphine)palladium (105 mg, 0.09 mmol) and an aqueous solution of potassium phosphate (2 M, 1.8 mL). The mixture was flushed with nitrogen for 10 min, and then stirred with heating at 90° C. under nitrogen overnight. After cooling to RT, the reaction mixture was partitioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate (50 mL×3). The combined organic layers were washed with brine, dried (Na2SO4), concentrated under reduced pressure and purified by column chromatography on silica gel to give 2,5-difluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)aniline (335 mg, 63% yield). 1H NMR (300 MHz, DMSO-d6): δ 8.35 (d, J=5.7 Hz, 1H), 8.27 (s, 1H), 7.98 (s, 1H), 7.24-7.18 (m, 2H), 6.75 (dd, J=12.3, 8.1 Hz, 1H), 6.62 (dd, J=5.4, 2.1 Hz, 1H), 5.53 (br s, 2 E), 3.87 (s, 3H); MS (ESI): m/z 303.1 [M+1]+.

1. customThe mixture was flushed with nitrogen for 10 min
2. temperatureAfter cooling to RT
3. customthe reaction mixture was partitioned between water and ethyl acetate
4. extractionThe aqueous layer was extracted with ethyl acetate (50 mL×3)
5. washThe combined organic layers were washed with brine
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated under reduced pressure
8. custompurified by column chromatography on silica gel