Reaction Steps
A mixture of N-(5-bromo-2-(2-methoxyphenyl)pyridin-3-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-amine (84.1 mg, 0.158 mmol), 2-dicyclohexylphosphino-2,4,6,-triisopropylbiphenyl, (X-Phos) (16.6 mg, 0.035 mmol), tris(dibenzylideneacetone)dipalladium (0) (15.4 mg, 0.017 mmol), morpholine (0.03 mL, 0.345 mmol), and sodium tert-butoxide (47.8 mg, 0.5 mmol) in dry toluene (5 mL) was degassed by nitrogen. The mixture was heated to 100° C. After 23 h, the reaction was cooled to rt, then treated with water. After extracting twice with EtOAc, the organic layer was combined and dried over anhydrous magnesium sulfate. After filtration and concentration, the residue was purified on basic alumina (5-20% EtOAc in hexanes) to afford an impure orange residue. The light orange film was further purified with SFC chromatography to afford 5,7-difluoro-N-(2-(2-methoxyphenyl)-5-morpholinopyridin-3-yl)-3-methyl-2-(pyridin-2-yl)quinolin-4-amine. 1H NMR (400 MHz, CDCl3) δ ppm 8.67 (1H, ddd, J=4.9, 1.8, 1.0 Hz), 8.10 (1H, d, J=2.5 Hz), 7.92 (1H, m), 7.75 (1H, d, J=7.8 Hz), 7.57 (1H, ddd, J=9.7, 2.5, 1.3 Hz), 7.49 (1H, dd, J=7.4, 1.8 Hz), 7.46 (1H, m), 7.34 (1H, ddd, J=7.6, 4.8, 1.3 Hz), 7.13 (1H, td, J=7.4, 1.0 Hz), 7.08 (1H, m), 6.96 (1H, ddd, J=13.4, 8.7, 2.3 Hz), 6.65 (1H, m), 3.95 (3H, s), 3.90 (4H, m), 3.29 (4H, m), 1.94 (3H, br. s.) Mass Spectrum (pos.) m/e: 540.3 (M+1).
