Methane → tert-Butyl 8-(4-(4-fluorobenzyloxy)-2-oxopyridin-1(2H)-yl)-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H) carboxylate

Participants

Reaction Conditions

Reaction Steps

A suspension of 4-(4-fluorobenzyloxy)pyridin-2(1H)-one (79 mg, 0.36 mmol), tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate (150 mg, 0.40 mmol), 8-hydroxyquinoline (11 mg, 0.072 mmol) and Cs2CO3 (129 mg, 0.40 mmol) in DMSO (10 mL) was degassed under reduced pressure for 40 min. CuI (82 mg, 0.43 mmol) was added to the above solution, and the reaction mixture was degassed under reduced pressure for 2×5 min. 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 5 min. Celite was added, and the suspension was stirred for 5 min. The suspension was filtered through Celite, and the filtrate was washed with brine. The resulting solution was dried over Na2SO4 and concentrated under reduced pressure. Purification by preparative TLC (DCM/MeOH/concentrated ammonia 98:1.8:0.2) gave partially purified product, which was dissolved in DCM and stirred with charcoal for 10 min. The suspension was filtered, and the filtrate was concentrated under reduced pressure to afford the title compound (0.12 g, 64%) as a yellow solid: 1H NMR (500 MHz, CDCl3) δ 7.52 (t, J=8.0 Hz, 1H), 7.41 (dd, J=8.5, 5.5 Hz, 2H), 7.31 (d, J=7.5 Hz, 1H), 7.24 (s, 1H), 7.10 (t, J=8.5 Hz, 2H), 7.00 (d, J=8.5 Hz, 1H), 6.07 (s, 1H), 6.02 (dd, J=7.5, 2.0 Hz, 1H), 5.01 (s, 2H), 3.78-3.63 (m, 4H), 3.64 (s, 3H), 3.05-2.98 (m, 4H), 1.50-1.48 (m, 9H).

Provenance & Evidence