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

Participants

Reaction Steps

The Buchwald coupled product was prepared according to Procedure H using dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.023 g, 0.048 mmol), 5-morpholinopyridin-3-amine (0.064 g, 0.36 mmol), 5-(4-chloro-5,7-difluoro-3-methylquinolin-2-yl)-N,N-dimethylpyridin-2-amine (0.1 g, 0.30 mmol) and Pd2dba3 (0.011 g, 0.012 mmol) and sodium tert-butoxide (0.072 g, 0.75 mmol) in toluene (3.0 mL) at 100° C. for 2 h. The crude product was purified by column chromatography on silica gel (0 to 100% DCM/MeOH/ammonium hydroxide (90/9/1)) to give the desired product 2-(6-(dimethylamino)pyridin-3-yl)-5,7-difluoro-3-methyl-N-(5-morpholinopyridin-3-yl)quinolin-4-amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.44 (2H, m), 7.87 (1H, dd, J=8.8, 2.5 Hz), 7.79 (1H, d, J=2.3 Hz), 7.56-7.59 (2H, m), 7.36 (1H, ddd, J=12.6, 9.5, 2.5 Hz), 6.76 (1H, d, J=8.8 Hz), 6.55 (1H, t, J=2.2 Hz), 3.70 (4H, m), 3.11-3.06 (10H, m), 2.19 (3H, s). Mass Spectrum (ESI) m/e=477.2 (M+1).

Provenance & Evidence