反应详情

温度

120 °C

To a stirred solution of dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (27.0 mg, 0.056 mmol), 2,5-dimorpholinopyridin-3-amine (37.0 mg, 0.140 mmol), 2,5-dimorpholinoaniline (55.0 mg, 0.21 mmol), 4-chloro-5-fluoro-3,8-dimethyl-2-(pyridin-2-yl)quinoline (100.0 mg, 0.35 mmol) and Pd2dba3 (13.0 mg, 0.014 mmol) in toluene (3.5 mL) was added sodium t-butoxide (84.0 mg, 0.87 mmol). The reaction mixture was heated to 120° C. and stirred for 45 min. The reaction was cooled to rt and diluted with water (25 mL). The mixture was extracted with EtOAc (3×10 mL) and DCM (1×10 mL). The organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (0 to 100% EtOAc in DCM) to give the desired products N-(2,5-di-4-morpholinylphenyl)-5-fluoro-3,8-dimethyl-2-(2-pyridinyl)-4-quinolinamine. 1H NMR (400 MHz, CDCl3) δ ppm 8.69 (1H, br. m.), 8.22 (1H br m), 8.02-8.12 (1H, m), 7.89 (1H, br. m.), 7.40 (2H, m), 7.28 (1H, m), 6.98-7.15 (2H, m), 6.24 (1H, br. s.), 3.87-4.00 (4H, br m), 3.80 (4H, br m), 3.09 (8H, br. m.), 2.77 (3H, s), 2.32 (3H, s); Mass Spectrum (ESI) m/e=514.3 (M+1). Further elution gave N-(2,5-di-4-morpholinyl-3-pyridinyl)-5-fluoro-3,8-dimethyl-2-(2-pyridinyl)-4-quinolinamine. 1H NMR (400 MHz, CDCl3) δ ppm 8.68 (1H, ddd, J=4.9, 1.8, 1.0 Hz), 8.08 (1H, d, J=7.8 Hz), 7.90 (1H, m), 7.82 (1H, br d), 7.60 (1H, d, J=2.5 Hz), 7.40-7.48 (1H, m), 7.37 (1H, m), 7.07 (1H, dd, J=13.6, 7.9 Hz), 6.47 (1H, br. s.), 3.88-4.00 (4H, m), 3.75-3.85 (4H, m), 3.23 (4H, br. s.), 3.03-3.13 (4H, m), 2.78 (3H, s), 2.31 (3H, s); Mass Spectrum (ESI) m/e=515.2 (M+1).

1. temperatureThe reaction was cooled to rt
2. extractionThe mixture was extracted with EtOAc (3×10 mL) and DCM (1×10 mL)
3. dry with materialThe organic layers were dried over magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe crude product was purified by column chromatography on silica gel (0 to 100% EtOAc in DCM)