8-Hydroxyquinoline → tert-Butyl 6-methyl-8-(2-oxo-4-(5-(trifluoromethyl)pyridin-2-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-(5-(trifluoromethyl)pyridin-2-yl)pyridin-2(1H)-one (178 mg, 0.740 mmol), tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate (255 mg, 0.673 mmol), CuI (154 mg, 0.808 mmol), 8-hydroxyquinoline (20 mg, 0.14 mmol) and Cs2CO3 (241 mg, 0.740 mmol) in DMSO (10 mL) was degassed under reduced pressure for 45 min. The suspension was put under Ar and stirred at 135° C. for 36 h. The suspension was cooled, 9:0.9:0.1 CH2Cl2/MeOH/NH4OH was added and the resulting suspension was stirred at 25° C. for 20 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 (133 mg, 33%) as a yellow solid: 1H NMR (300 MHz, CDCl3) δ 9.00 (br s, 1H), 8.07 (br d, J=8.3 Hz, 1H), 7.91 (d, J=8.3 Hz, 1H), 7.60-7.52 (m, 2H), 7.32 (s, 1H), 7.28-7.20 (overlapping with solvent peak, 1H), 7.11-7.02 (m, 2H), 3.84-3.60 (m, 7H), 3.12-2.95 (m, 4H), 1.49 (s, 9H).

Provenance & Evidence