反应详情

The Buchwald coupled product was 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, 0.31 mmol), 4-chloro-7-fluoro-3-methyl-2-(4-methylpyridin-2-yl)quinoline (0.075 g, 0.26 mmol), Pd2dba3 (9.58 mg, 10.46 μmol) and sodium tert-butoxide (0.063 g, 0.65 mmol) in toluene (2.6 mL) at 120° C. for 4.6 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)-7-fluoro-3-methyl-2-(4-methylpyridin-2-yl)-quinolin-4-amine. 1H NMR (400 MHz, CDCl3) δ ppm 8.58 (2H, d, J=5.1 Hz), 7.81 (2H, m), 7.69 (1H, s), 7.59 (1H, m), 7.32-7.25 (1H, m), 7.22 (1H, d, J=4.9 Hz), 6.74 (1H, s), 6.21 (1H, m), 3.92 (4H, t, J=4.7 Hz), 3.74 (4H, app t, J=5.0, 4.7 Hz), 3.23 (4H, br. s.), 2.92 (6H, app t, J=4.7 Hz), 2.49 (3H, s), 2.36 (3H, s). Mass Spectrum (ESI) m/e=515.2 (M+1).

1. customwas prepared
2. customat 120° C.
3. customfor 4.6 h
4. customThe crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc)