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

関与物質

反応条件

反応手順

A suspension of 4-(6-(trifluoromethyl)pyridazin-3-yl)pyridin-2(1H)-one (78 mg, 0.32 mmol), tert-butyl 8-bromo-6-tosyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate (183 mg, 0.353 mmol), CuI (73 mg, 0.39 mmol), 8-hydroxyquinoline (9 mg, 0.06 mmol) and Cs2CO3 (115 mg, 0.353 mmol) in DMSO (10 mL) was degassed under reduced pressure for 45 min. The suspension was put under N2 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 (95 mg, 44%) as a yellow viscous oil: 1H NMR (300 MHz, CDCl3) δ 8.35 (br s, 1H), 8.12 (d, J=8.9 Hz, 1H), 7.99 (d, J=8.9 Hz, 1H), 7.71-7.63 (m, 4H), 7.54-7.47 (m, 1H), 7.39-7.22 (m, 4H), 3.73-3.58 (m, 4H), 3.44-3.31 (m, 2H), 2.95-2.86 (m, 2H), 2.37 (s, 3H), 1.47 (s, 9H).

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