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

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.023 g, 0.047 mmol), 2,5-dimorpholinopyridin-3-amine (0.094 g, 0.354 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(3-methylpyridin-2-yl)quinoline (0.090 g, 0.295 mmol) and Pd2dba3 (10.8 mg, 0.012 mmol) in toluene (3.00 mL) was added sodium t-butoxide (0.071 g, 0.738 mmol). The reaction mixture was heated to 120° C. for 2 h. After which the reaction was 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-(3-methyl-2-pyridinyl)-4-quinolinamine. 1H NMR (400 MHz, CDCl3) δ ppm 8.56 (1H, d, J=4.5 Hz), 7.71 (2H, m), 7.62 (2H, d, J=2.5 Hz), 7.35 (1H, m), 7.02 (1H, m), 6.39 (1H, br. s.), 3.93 (4H, br. s.), 3.76-3.87 (4H, m), 3.23 (4H, br. s.), 3.05 (4H, br. s.), 2.28 (3H, s), 1.95 (3H, br. s.). Mass Spectrum (ESI) m/e=533.2 (M+1).

Provenance & Evidence