反应详情

温度

90 °C

A solution of Example A1 (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 DMF (30 mL) was treated with tetrakis(triphenylphosphine)palladium(0) [Pd(PPh3)4] (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 heated at 90° C. overnight. After cooling to RT, the mixture was treated with water, extracted with EtOAc (4×) and the combined organics were washed with brine, dried (Na2SO4), concentrated under reduced pressure and purified by silica gel chromatography to give 2,5-difluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)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, 2H), 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. additionthe mixture was treated with water
4. extractionextracted with EtOAc (4×)
5. washthe combined organics were washed with brine
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated under reduced pressure
8. custompurified by silica gel chromatography