2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → N-(2,5-di(4-morpholinyl)-3-pyridinyl)-5,7-difluoro-3-methyl-2-(1-methyl-1H-indol-5-yl)-4-quinolinamine

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.022 g, 0.047 mmol), 2,5-dimorpholinopyridin-3-amine (0.093 g, 0.350 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(1-methyl-1H-indol-5-yl)quinoline (0.1 g, 0.292 mmol) and Pd2dba3 (10.7 mg, 0.012 mmol) in toluene (2.92 mL) was added sodium t-butoxide (0.070 g, 0.73 mmol). The reaction mixture was heated to 120° C. and stirring continued for 2 h. 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-(1-methyl-1H-indol-5-yl)-4-quinolinamine. 1H NMR (400 MHz, CDCl3) δ ppm 7.87 (1H, s), 7.66 (3H, m), 7.46 (2H, s), 7.15 (1H, d, J=3.1 Hz), 6.94-7.04 (1H, m), 6.57 (1H, d, J=2.9 Hz), 6.43 (1H, br. s.), 3.89-3.96 (4H, m), 3.88 (3H, s), 3.83-3.87 (4H, m), 3.30 (4H, br s), 3.03-3.14 (4H, m), 2.20 (3H, s). Mass Spectrum (ESI) m/e=571.3 (M+1).

Provenance & Evidence