反应详情

温度

100 °C

A mixture of 4-(3,3,7-trimethylindolin-6-yl)morpholine (37.9 mg, 0.154 mmol), 4,6-dichloro-7-methoxy-2,3-dimethylquinoline (made by procedures A-D, 59.1 mg, 0.231 mmol), cesium carbonate (75.3 mg, 0.231 mmol), Pd2(dba)3 (28.4 mg, 0.031 mmol), and Xantphos (26.7 mg, 0.046 mmol) in toluene (2 mL) under N2 was heated at 100° C. for 21 h. The mixture was cooled to rt and diluted with DCM-MeOH (8:2). The mixture was filtered and the filtrates were concentrated. Purification of the residue by flash chromatography over silica gel, using 40% EtOAc in hexane, and following the second purification by flash chromatography over silica gel, using 10% MeOH in DCM, gave 6-chloro-7-methoxy-2,3-dimethyl-4-(3,3,7-trimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-indol-1-yl)quinoline. 1H-NMR (DMSO-d6) δ 7.40 (1H, s), 7.09 (1H, s), 7.07 (1H, d, J=8.0 Hz), 6.72 (1H, d, J=8.0 Hz), 4.01 (3H, s), 3.93 (1H, d, J=8.0 Hz), 3.80-3.62 (4H, m), 3.53 (1H, d, J=8.0 Hz), 3.00-2.90 (2H, m), 2.75-2.69 (2H, m), 2.61 (3H, s), 2.42 (3H, s), 1.70 (3H, s), 1.33 (3H, s), 1.09 (3H, s). Mass Spectrum (ESI) m/e=466.1 (M+1).

1. temperatureThe mixture was cooled to rt
2. filtrationThe mixture was filtered
3. concentrationthe filtrates were concentrated
4. customPurification of the residue by flash chromatography over silica gel
5. customthe second purification by flash chromatography over silica gel