8-Hydroxyquinoline → tert-Butyl 6-methyl-8-(2-oxo-4-(6-(trifluoromethyl)pyridazin-3-yl)pyridin-1 (2H)-yl)-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate

Participants

Reaction Conditions

Reaction Steps

A suspension of 4-(6-(trifluoromethyl)pyridazin-3-yl)pyridin-2(1H)-one (106 mg, 0.438 mmol), tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate (183 mg, 0.482 mmol), CuI (100 mg, 0.526 mmol), 8-hydroxyquinoline (13 mg, 0.09 mmol) and Cs2CO3 (157 mg, 0.482 mmol) in DMSO (10 mL) was degassed under reduced pressure for 45 min. The suspension was put under Ar and stirred at 135° C. overnight. The suspension was cooled, 9:0.9:0.1 CH2Cl2/MeOH/NH4OH (10 mL) was added and the resulting suspension was stirred at 25° C. for 30 min. The suspension was passed through a plug of silica gel and the filtrate was washed with brine. The resulting solution was dried over Na2SO4 and concentrated under reduced pressure. Flash chromatography (silica gel, (1:1 EtOAc/hexanes)/(9:0.9:0.1 CH2Cl2/MeOH/NH4OH), 100:0 to 0:100) afforded the title compound (74 mg, 30%) as a viscous oil: 1H NMR (300 MHz, CDCl3) δ 8.10 (d, J=8.7 Hz, 1H), 7.97 (d, J=8.7 Hz, 1H), 7.65 (d, J=6.9 Hz, 1H), 7.62-7.53 (m, 1H), 7.33 (br s, 1H), 7.30-7.21 (overlapping with solvent peak, 2H), 7.08 (d, J=8.1 Hz, 1H), 3.71-3.62 (m, 7H), 3.11-2.98 (m, 4H), 1.49 (s, 9H).

Provenance & Evidence