反应详情

The Buchwald coupled product was prepared according to Procedure H using dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.016 g, 0.034 mmol), 2,5-dimorpholinopyridin-3-amine (0.067 g, 0.25 mmol), 2-(2,4-bis(trifluoromethyl)phenyl)-4-chloro-5,7-difluoro-3-methylquinoline (0.090 g, 0.21 mmol), Pd2dba3 (7.74 mg, 8.46 μmol) and sodium tert-butoxide (0.051 g, 0.53 mmol) in toluene (2.1 mL) at 120° C. for 75 h. The crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc) to give the desired product 2-(2,4-bis(trifluoromethyl)phenyl)-N-(2,5-dimorpholinopyridin-3-yl)-5,7-difluoro-3-methylquinolin-4-amine. 1H NMR (400 MHz, CDCl3) δ ppm 8.10 (1H, s), 7.98 (1H, d, J=8.0 Hz), 7.81 (1H, br. s), 7.62 (1H, J=2.4 Hz), 7.59-7.54 (2H, m), 7.10 (1H, ddd, J=13.3, 8.4, 2.5 Hz), 6.24 (1H, br. s.), 3.93 (4H, m), 3.79 (4H, app t, J=4.7 Hz), 3.40 (4H, br. s.), 3.01 (4H, app t, J=4.9 Hz), 1.92 (3H, s). Mass Spectrum (ESI) m/e=654.3 (M+1).

1. customwas prepared
2. customat 120° C.
3. customfor 75 h
4. customThe crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc)