反应详情

The Buchwald coupled product was prepared according to Procedure H using dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.024 g, 0.05 mmol), 2,5-dimorpholinopyridin-3-amine (0.098 g, 0.37 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(pyridin-3-yl)quinoline (0.090 g, 0.31 mmol), Pd2dba3 (0.011 g, 0.012 mmol) and sodium tert-butoxide (0.074 g, 0.77 mmol) in toluene (3.1 mL) at 120° C. for 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-(pyridin-3-yl)quinolin-4-amine. 1H NMR (400 MHz, CDCl3) δ ppm 8.86 (1H, d, J=2.3 Hz), 8.73 (1H, dd, J=4.9, 1.8 Hz), 7.99 (1H, dt, J=7.8, 2.0 Hz), 7.76 (1H, d, J=11.2 Hz), 7.67 (1H, d, J=2.7 Hz), 7.62 (1H, br d, J=9.0 Hz), 7.50 (1H, dd, J=7.8, 4.9 Hz), 7.04 (1H, ddd, J=13.3, 8.4, 2.4 Hz), 6.37 (1H, d, J=2.2 Hz), 3.91 (4H, m), 3.82 (4H, app t, J=4.1 Hz), 3.23 (4H, br. s.), 3.05 (4H, app t, J=4.3 Hz), 2.18 (3H, s). Mass Spectrum (ESI) m/e=519.2 (M+1).

1. customwas prepared
2. customat 120° C.
3. customfor 5 h
4. customThe crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc)