反应详情

温度

70 °C

A mixture of N-(4-((2-chloropyridin-4-yl)oxy)-2,5-difluorophenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (0.101 g, 0.214 mmol), 1-(2-((tert-butyldimethylsilyl)oxy)ethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.098 g, 0.278 mmol) and K2CO3 (0.089 g, 0.642 mmol) in dioxane (2 mL) and H2O (0.333 mL) was sparged with Ar, treated with Pd(PPh3)4 (0.012 g, 10.70 μmol), sparged with Ar again, and heated to 70° C. overnight. The mixture was cooled to RT, treated with satd. NaHCO3, extracted with EtOAc (2×) and the combined organics were washed with brine, dried over MgSO4, concentrated to dryness and purified via silica gel chromatography (EtOAc/Hex) to afford N-(4-((2-(1-(2-((tert-butyldimethylsilyl)oxy)ethyl)-1H-pyrazol-4-yl)pyridin-4-yl)oxy)-2,5-difluorophenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (124 mg, 88%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 12.44 (s, 1H); 8.58-8.59 (m, 2H); 8.39 (d, J=5.7 Hz, 1H); 8.23 (s, 1H); 8.16 (dd, J=6.6, 2.2 Hz, 1H); 8.01 (s, 1H); 7.60-7.62 (m, 3H); 7.43 (m, 2H); 7.19 (d, J=2.5 Hz, 1H); 6.43-6.75 (m, 2H); 4.18 (t, J=5.1 Hz, 2H); 3.89 (t, J=5.2 Hz, 2H); 0.75 (s, 9H); −0.12 (s, 6H); MS (ESI) m/z: 662.3 (M+H+).

1. customwas sparged with Ar
2. customsparged with Ar again
3. temperatureThe mixture was cooled to RT
4. additiontreated with satd
5. extractionNaHCO3, extracted with EtOAc (2×)
6. washthe combined organics were washed with brine
7. dry with materialdried over MgSO4
8. concentrationconcentrated to dryness
9. custompurified via silica gel chromatography (EtOAc/Hex)