2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → N-(2,5-dimorpholinopyridin-3-yl)-5,7-difluoro-3-methyl-2-(6-(piperidin-1-yl)-pyridin-3-yl)quinolin-4-amine

Participants

Reaction Steps

The Buchwald coupled product was prepared according to Procedure S using dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.020 g, 0.043 mmol), 2,5-dimorpholinopyridin-3-amine (0.085 g, 0.32 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(6-(piperidin-1-yl)pyridin-3-yl)quinoline (0.1 g, 0.268 mmol), Pd2dba3 (0.010 g, 0.011 mmol) and sodium tert-butoxide (0.064 g, 0.67 mmol) in toluene (2.7 mL) at 100° C. for 19 h. The crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc) to give the desired product N-(2,5-dimorpholinopyridin-3-yl)-5,7-difluoro-3-methyl-2-(6-(piperidin-1-yl)-pyridin-3-yl)quinolin-4-amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.44 (1H, dd, J=2.5, 0.4 Hz), 7.84 (1H, dd, J=8.9, 2.4 Hz), 7.74 (1H, d, J=6.3 Hz), 7.59 (1H, m), 7.55 (1H, d, J=2.7 Hz), 7.36-7.44 (1H, m), 6.94 (1H, d, J=9.0 Hz), 6.40 (1H, d, J=2.7 Hz), 3.78-3.59 (12H, m), 3.13 (2H, br. s.), 2.94-3.04 (4H, m), 2.84 (2H, br. s.), 2.13 (3H, s), 1.64 (2H, m), 1.57 (4H, m). Mass Spectrum (ESI) m/e=602.3 (M+1).

Provenance & Evidence