反应详情

The Buchwald coupled product was prepared according to Procedure H using dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.023 g, 0.048 mmol), 2,5-dimorpholinopyridin-3-amine (0.095 g, 0.36 mmol), 5-(4-chloro-5,7-difluoro-3-methylquinolin-2-yl)-N,N-dimethylpyridin-2-amine (0.1 g, 0.30 mmol), Pd2dba3 (0.011 g, 0.012 mmol) and sodium tert-butoxide (0.072 g, 0.75 mmol) in toluene (3.0 mL) at 100° C. for 2 h. The crude product was purified by column chromatography on silica gel (0 to 100% DCM/MeOH/ammonium hydroxide (90/9/1)) to give the desired product 2-(6-(dimethylamino)pyridin-3-yl)-N-(2,5-dimorpholinopyridin-3-yl)-5,7-difluoro-3-methylquinolin-4-amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.44 (1H, dd, J=2.4, 0.6 Hz), 7.85 (1H, dd, J=8.9, 2.4 Hz), 7.74 (1H, d, J=5.9 Hz), 7.57-7.63 (1H, m), 7.55 (1H, d, J=2.7 Hz), 7.34-7.45 (1H, m), 6.78 (1H, d, J=8.4 Hz), 6.40 (1H, d, J=2.5 Hz), 3.61-3.80 (8H, m), 3.16 (2H, br. s.), 3.11 (6H, s), 2.95-3.02 (4H, m), 2.13 (3H, s). Mass Spectrum (ESI) m/e=562.3 (M+1).

1. customwas prepared
2. customat 100° C.
3. customfor 2 h
4. customThe crude product was purified by column chromatography on silica gel (0 to 100% DCM/MeOH/ammonium hydroxide (90/9/1))