反应详情

The Buchwald coupled product was prepared according to Procedure S using of 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-(2-(piperazin-1-yl)pyridin-4-yl)quinoline (0.1 g, 0.27 mmol) and 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 2 h. The crude product was purified by column chromatography on silica gel (0 to 100% DCM/methanol/ammonium hydroxide (90/9/1)) to give the desired product N-(2,5-dimorpholinopyridin-3-yl)-5,7-difluoro-3-methyl-2-(2-(piperazin-1-yl)pyridin-4-yl)quinolin-4-amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.25 (1H, d, J=5.1 Hz), 7.81 (1H, d, J=6.3 Hz), 7.62-7.66 (1H, m), 7.55 (1H, d, J=2.5 Hz), 7.46-7.53 (1H, m), 6.91 (1H, s), 6.81 (1H, dd, J=5.0, 1.1 Hz), 6.45 (1H, d, J=2.5 Hz), 3.65 (8H, m), 3.44-3.53 (4H, m), 3.32 (4H, m), 3.00 (4H, br. s.), 2.78-2.88 (4H, m), 1.99 (3H, s). Mass Spectrum (ESI) m/e=603.3 (M+1).

1. customwas prepared
2. customThe crude product was purified by column chromatography on silica gel (0 to 100% DCM/methanol/ammonium hydroxide (90/9/1))