8-Hydroxyquinoline → HCID 57950282, compound

Participants

Reaction Conditions

Reaction Steps

tert-Butyl-7-bromo-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (0.35 g, 0.96 mmol), 4-(4-methoxy-2-methylphenyl)pyridin-2(1H)-one (0.21 g, 0.96 mmol) and Cs2CO3 (0.35 g, 1.1 mmol) were suspensed in DMSO (5.6 mL), and the resulting suspension was degassed under vacuum for 15 min. The system was then flushed with Ar, and 8-hydroxyquinoline (42 mg, 0.29 mmol) and copper iodide (0.22 g, 1.2 mmol) were added. The evacuation/Ar flushing process was repeated twice more, and the reaction mixture was heated at 130° C. for 18 h under N2. The suspension was cooled, diluted with 20% NH4OH/MeOH (10 mL) and stirred at ambient temperature for 30 min. The reaction was further diluted with CH2Cl2 (100 mL). The solution was filtered through silica gel and concentrated. The concentrate was diluted with CH2Cl2 and washed with brine (4×20 mL). The organic phase was dried over Na2SO4 and concentrated to dryness under reduced pressure. Flash column chromatography (12 g ISCO column, (1:1 hexanes/EtOAc)/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 5 column volumes, increased to 50:50 over 20 column volumes and then hold for 5 column volumes, increase to 0:100 over 10 column volumes and hold for 5 column volumes) gave the title compound (0.25 g, 52%) as a yellow film: 1H NMR (500 MHz, CDCl3) δ 7.54 (d, J=8.0 Hz, 1H), 7.42 (d, J=6.5 Hz, 1H), 7.39 (d, J=1.5 Hz, 1H), 7.22 (d, J=8.0 Hz, 1H), 7.10 (d, J=7.0 Hz, 1H), 6.82-6.80 (m, 2H), 6.60 (d, J=1.5 Hz, 1H), 6.24 (dd, J=6.5, 1.5 Hz, 1H), 4.67-4.65 (m, 2H), 3.86-3.83 (m, 5H), 3.65 (s, 3H), 2.93 (m, 3H), 2.82-2.84 (m, 2H), 1.50 (s, 9H).

Provenance & Evidence