8-Hydroxyquinoline → HCID 66873656, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of 4-(6-(trifluoromethyl)pyridin-3-yl)pyrimidin-2(1H)-one (69 mg, 0.29 mmol), tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate (120 mg, 0.32 mmol), 8-hydroxyquinoline (8.4 mg, 0.058 mmol) and Cs2CO3 (110 mg, 0.35 mmol) in DMSO (5.0 mL) was degassed under reduced pressure for 30 min. CuI (66.7 mg, 0.35 mmol) was then added to the above solution, and the reaction mixture was degassed under reduced pressure for 5 min. The suspension was then stirred at 135° C. under nitrogen overnight. The suspension was cooled and diluted with ethyl acetate. The resulting mixture was washed with aqueous LiCl (5%), ammonium hydroxide (2×), and brine. The organic extract was separated, dried over sodium sulfate, and concentrated under reduced pressure. The resulting crude material was purified by preparative TLC (hexanes/ethyl acetate 1:1 then DCM/MeOH 96:4). The desired band was collected and extracted with dichloromethane. The resulting solution was treated with charcoal, filtered through a pad of celite, and concentrated under reduced pressure to give the title compound (36 mg, 20%) as a yellow foam: 1H NMR (500 MHz, CDCl3) δ 9.36 (s, 1H), 8.76 (d, J=7.0 Hz, 1H), 8.99 (d, J=6.5 Hz, 1H), 7.86 (d, J=8.5 Hz, 1H), 7.58-7.56 (m, 1H), 7.38-7.37 (m, 1H), 7.09-7.08 (m, 1H), 6.93 (d, J=7.0 Hz, 1H), 3.80-3.68 (m, 4H), 3.68 (s, 3H), 3.09-2.99 (m, 4H), 1.49 (s, 9H).

Provenance & Evidence