Reaction Steps
A suspension of diethyl (4-{[4-{[4-bromo-5-fluoro-2-(methylcarbamoyl)phenyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (Compound 7C, 400 mg, 0.60 mmol), 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propan-1-ol (Compound 3E 258 mg, 1.02 mmol), [1,1-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (49.17 mg, 0.06 mmol), and potassium carbonate (252 mg, 1.82 mmol) in 1,4-Dioxane (2 mL) and H2O (0.5 mL) was evacuated and purged with nitrogen (3×). The sample was irradiated in the microwave at 100° C. for 1.5 hours. The reaction mixture was filtered. The filtrate was quenched with water (10 mL) and extracted with EtOAc (20 mL). The organic layer was washed with brine (15 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to a brown oil. The crude material was purified on a Teledyne ISCO Combiflash® Rf system using DCM/MeOH (100:0→85:15) to afford the title compound as 345 mg of a yellow solid (81%). 1H NMR (DMSO-d6, 400 MHz): δ=11.84 (s, 1H), 8.94 (s, 1H), 8.80 (d, J=4.8 Hz, 1H), 8.45 (s, 1H), 8.39 (s, 1H), 8.16 (d, J=1.5 Hz, 1H), 8.04 (d, J=8.6 Hz, 1H), 7.94 (s, 1H), 7.53 (d, J=7.8 Hz, 1H), 7.02 (s, 1H), 6.86 (ddd, J=1.8, 2.2, 8.4 Hz, 1H), 4.62 (t, J=5.1 Hz, 1H), 4.23 (t, J=7 Hz, 2H), 3.91-4.00 (m, 4H), 3.78 (s, 3H), 3.39-3.45 (m, 2H), 3.19-3.27 (m, 2H), 2.81 (d, J=4.6 Hz, 3H), 1.96 (quin, J=6.6 Hz, 2H), 1.16 (t, J=7.1 Hz, 6H). MS (ESI): m/z 710.22 [M+H]+. UPLC: tR=1.42 min (UPLC-TOF: polar—3 min).
