8-Hydroxyquinoline → tert-butyl 6-methyl-8-(2-oxo-4-phenethylpyrimidin-1(2H)-yl)-3,4,5,6-tetrahydroazepino[4,3-b]indole-2(1H) carboxylate

Participants

Reaction Conditions

Reaction Steps

A suspension of 4-phenethylpyrimidin-2(1H)-one (55 mg, 0.28 mmol), tert-butyl 8-bromo-6-methyl-3,4,5,6-tetrahydroazepino[4,3-b]indole-2(1H) carboxylate (0.13 g, 0.34 mmol), 8-hydroxyquinoline (10 mg, 0.07 mmol) and Cs2CO3 (0.12 g, 0.36 mmol) in DMSO (4.5 mL) was degassed under reduced pressure for 15 min. CuI (65.0 mg, 0.34 mmol) was added to the above solution, and the reaction mixture was degassed under reduced pressure for 5 min. The suspension was heated at 135° C. in a microwave for 150 min. The mixture was then cooled and diluted with ethyl acetate. The resulting mixture was washed sequentially with an aqueous solution of LiCl (5%) and ammonium hydroxide (1%) (2×) and brine. The organic extract was separated, dried over sodium sulfate and concentrated under reduced pressure. The crude material was dissolved in DCM, treated with charcoal for 20 min and filtered through a pad of celite. The filtrate was concentrated under reduced pressure, and the residue was purified by flash column chromatography (DCM to DCM/MeOH 95:5) to give the title compound (34.0 mg, 25%) as a yellow oil: 1H NMR (500 MHz, CDCl3) δ 7.67-7.53 (m, 2H), 7.33-7.20 (m, 6H), 7.05-6.98 (m, 1H), 6.22 (d, J=6.5 Hz, 1H), 4.71-4.62 (m, 2H), 3.76-3.68 (m, 2H), 3.66 (s, 3H), 3.15-3.12 (m, 2H), 3.02-2.96 (m, 4H), 2.08-2.02 (m, 2H), 1.49-1.27 (m, 9H).

Provenance & Evidence