N-(4-(3-Bromopyridin-4-yloxy)-2,5-difluorophenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (0.119 g, 0.231 mmol) was combined with 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)acetonitrile (0.054 g, 0.231 mmol) and potassium carbonate (0.096 g, 0.692 mmol) in dioxane (4 mL) and water (0.667 mL), sparged with argon for several minutes, treated with tetrakis(triphenylphosphine)palladium(0) (0.013 g, 0.012 mmol) and heated to 85° C. overnight. The mixture was cooled to room temperature, treated with saturated NaHCO3 and extracted with EtOAc (2×). The combined organics were washed with brine, dried over MgSO4 and concentrated to dryness. The crude material was purified over silica gel (40-100% EtOAc/Hex) to afford N-(4-(3-(1-(cyanomethyl)-1H-pyrazol-4-yl)pyridin-4-yloxy)-2,5-difluorophenyl)-1-(4-Fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (30 mg, 24% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 12.45 (s, 1H); 8.91 (s, 1H); 8.61 (dd, J=7.4, 2.1 Hz, 1H); 8.55 (m, 1H); 8.44 (s, 1H); 8.29 (d, J=5.7 Hz, 1H); 8.24 (s, 1H); 8.16 (dd, J=6.6, 2.2 Hz, 1H); 7.67 (dd, J=11.0, 7.3 Hz, 1H); 7.60 (dd, J=8.7, 4.9 Hz, 2H); 7.42 (t, J=8.7 Hz, 2H); 6.75 (m, 2H); 5.54 (s, 2H); MS (ESI) m/z: 543.1 (M+H+).
