反应详情

The Buchwald prepared according to Procedure H using dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.020 g, 0.042 mmol), 2,5-dimorpholinopyridin-3-amine (0.083 g, 0.32 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(1-methyl-1H-indol-4-yl)quinoline (0.090 g, 0.26 mmol), Pd2dba3 (9.62 mg, 10.50 mmol) and sodium tert-butoxide (0.068 g, 0.71 mmol) in toluene (2.6 mL) at 120° C. for 3.5 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-(1-methyl-1H-indol-4-yl)quinolin-4-amine. 1H NMR (400 MHz, CDCl3) δ ppm 7.79 (3H, d, J=11.5 Hz), 7.65 (1H, m), 7.63 (1H, d, J=2.7 Hz), 7.45 (1H, d, J=8.2 Hz), 7.38 (1H, app t, J=8.2 Hz), 7.22 (1H, d, J=0.6 Hz), 7.09 (1H, d, J=3.1 Hz), 7.02 (3H, ddd, J=13.5, 8.6, 2.5 Hz), 6.41 (1H, d, J=2.3 Hz), 6.25 (1H, d, J=3.1 Hz), 3.93 (4H, br. s), 3.87 (3H, s), 3.84 (4H, m), 3.25 (4H, br. s), −3.07 (4H, br. s.), 2.03 (3H, s). Mass Spectrum (ESI) m/e=571.3 (M+1).

1. customThe Buchwald prepared
2. customat 120° C.
3. customfor 3.5 h
4. customThe crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc)