8-Hydroxyquinoline → tert-Butyl 7-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-9-tosyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate

Participants

Reaction Conditions

Reaction Steps

A suspension of 4-(benzyloxy)pyridin-2(1H)-one (426 mg, 2.12 mmol), tert-butyl 7-bromo-9-tosyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate (1.28 g, 2.54 mmol), CuI (484 mg, 2.54 mmol), 8-hydroxyquinoline (369 mg, 2.54 mmol) and Cs2CO3 (760 mg, 2.33 mmol) in DMSO (10 mL) was degassed under reduced pressure for 45 min. The suspension was put under Ar and heated at 135° C. with stirring for 1.5 h. The suspension was cooled, 4:1 CH2Cl2/(9:1 MeOH/NH4OH) (50 mL) was added and the resulting suspension was stirred at 25° C. for 10 min. The suspension was passed through a plug of silica gel and the filtrate was washed with brine. The solution was dried over Na2SO4 and concentrated under reduced pressure to afford an amorphous solid. Flash chromatography (silica gel, (1:1 EtOAc/hexanes)/(9:0.9:0.1 CH2Cl2/MeOH/NH4OH) 100:0 to 0:100) yielded the title compound (715 mg, 54%) as an off-white solid: 1H NMR (300 MHz, CDCl3) δ 8.18 (br s, 1H), 7.82-7.73 (m, 2H), 7.48-7.35 (m, 6H), 7.33-7.23 (m, 4H), 6.12-5.97 (m, 2H) 5.07 (s, 2H), 4.90 (br s, 2H), 3.72-3.64 (m, 2H), 2.73-2.63 (m, 2H), 2.34 (s, 3H), 1.51 (s, 9H).

Provenance & Evidence