8-Hydroxyquinoline → HCID 57950420, compound

Participants

Reaction Conditions

Reaction Steps

tert-Butyl-7-bromo-9-methyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate (0.328 g, 0.898 mmol), 4-(imidazo[1,2-a]pyridin-2-ylmethoxy)pyridine-2(1H)-one (0.240 g, 0.998 mmol) and Cs2CO3 (0.358 g, 1.09 mmol) were suspended in DMSO (4.0 mL), and argon was bubbled through the system for 10 minutes. 8-Hydroxyquinoline (43.4 mg, 0.299 mmol) and copper iodide (228 mg, 1.20 mmol) were added, and resulting suspension was placed under vacuum for 15 min. The system was flushed with argon. The evacuation/argon flushing process was repeated a total of three times. The reaction mixture was heated at 130° C. for 18 h under argon. The mixture was cooled, and a solution of 20% NH4OH in MeOH (40 mL) was added. The resulting mixture was stirred for 1 h. The mixture was diluted with CH2Cl2 and filtered through a silica gel plug. The filtrate was collected and concentrated. The residue was diluted with CH2Cl2, washed with brine (3×25 mL), dried over Na2SO4 and concentrated under reduced pressure. Purification by flash column chromatography (80 g ISCO column, (1:1 hexanes/EtOAc)/(80:18:2 CH2Cl2/MeOH/NH4OH), 80:20 to 0:100:0 over 10 column volumes and then hold for 8 column volumes) gave the title compound (0.190 g, 40%) as a yellow foam: 1H NMR (500 MHz, DMSO-d6) δ 8.12 (d, J=6.8 Hz, 1H), 7.69 (s, 1H), 7.61 (d, J=9.1 Hz, 1H), 7.52 (d, J=8.3 Hz, 1H), 7.31-7.29 (m, 2H), 7.22-7.19 (m, 1H), 7.02 (dd, J=8.3, 1.7 Hz, 1H), 6.83-6.80 (m, 1H), 6.17 (d, J=2.7 Hz, 1H), 6.07 (dd, J=7.6, 2.7 Hz, 1H), 5.25 (s, 2H), 4.64 (m, 2H), 3.75 (m, 2H), 3.63 (s, 3H), 2.80 (m, 2H), 1.52 (s, 9H), ESI MS m/z 526 [M+H]+.

Provenance & Evidence