2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → N-(2,5-di(4-morpholinyl)-3-pyridinyl)-5,7-difluoro-3-methyl-2-(4-methyl-2-pyridinyl)-4-quinolinamine

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.025 g, 0.053 mmol), 2,5-dimorpholinopyridin-3-amine (0.104 g, 0.39 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinoline (0.1 g, 0.33 mmol) and Pd2dba3 (0.012 g, 0.013 mmol) in toluene (3.28 mL) was added sodium t-butoxide (0.079 g, 0.820 mmol). The reaction mixture was heated to 120° C. and stirring continued for 2.5 h. The reaction was then cooled to rt and diluted with water (15 mL). The mixture was extracted with EtOAc (2×15 mL) and DCM (1×15 mL). The organic layers were combined and washed with brine (1×20 mL) and dried over magnesium sulfate. The crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc) to give the desired product N-(2,5-di(4-morpholinyl)-3-pyridinyl)-5,7-difluoro-3-methyl-2-(4-methyl-2-pyridinyl)-4-quinolinamine. 1H NMR (400 MHz, CDCl3) δ ppm 8.53 (1H, d, J=2.2 Hz), 7.81 (1H, d, J=7.8 Hz), 7.71 (2H, dd, J=7.6, 2.0 Hz), 7.63 (2H, d, J=2.5 Hz), 6.96-7.06 (1H, m), 6.45 (1H, br. s.), 3.92 (4H, br. s.), 3.78-3.87 (4H, m), 3.23 (4H, br. s.), 3.03-3.12 (4H, m), 2.45 (3H, s), 2.22 (3H, s). Mass Spectrum (ESI) m/e=533.2 (M+1).

Provenance & Evidence