反应详情

The Buchwald coupled product was prepared according to Procedure H using dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.025 g, 0.053 mmol), 2,5-dimorpholinopyridin-3-amine (0.106 g, 0.40 mmol), 4-chloro-7-fluoro-3-isopropyl-2-(4-methylpyridin-2-yl)quinoline (0.105 g, 0.33 mmol), Pd2dba3 (0.012 g, 0.013 mmol) and sodium tert-butoxide (0.080 g, 0.83 mmol) in toluene (3.3 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-isopropyl-2-(4-methylpyridin-2-yl)-quinolin-4-amine. 1H NMR (400 MHz, CDCl3) δ ppm 8.58 (1H, dd, J=5.1, 0.6 Hz), 7.96 (1H, br s), 7.55-7.62 (2H, m), 7.52 (1H, m), 7.22 (1H, m), 7.13 (1H, br s), 7.07 (2H, dd, J=4.6, 1.1 Hz), 6.19 (1H, s), 3.96-3.91 (4H, m), 3.71 (4H, m), 3.50 (2H, br. s.), 3.40 (1H, m), 3.00 (1H, br s), 2.86 (4H, t, J=4.8 Hz), 2.48 (3H, s), 1.52 (3H, d, J=7.4 Hz), 1.13 (3H, d, J=7.4 Hz). Mass Spectrum (ESI) m/e=543.2 (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)