8-Hydroxyquinoline → HCID 70805297, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of tert-butyl 8-bromo-6-methyl-3,4,5,6-tetrahydroazepino[4,3-b]indole-2(1H)-carboxylate (105 mg, 0.28 mmol), 4-(6-(trifluoromethyl)pyridin-3-yl)pyrimidin-2(1H)-one (50 mg, 0.18 mmol), 8-hydroxyquinoline (6 mg, 0.04 mmol) and Cs2CO3 (0.12 g, 0.37 mmol) in DMSO (5.0 mL) was degassed under reduced pressure for 30 min. CuI (61.9 mg, 0.33 mmol) was added to the above solution, and the reaction mixture was degassed under reduced pressure for 5 min. Triethylamine (0.025 mL, 0.18 mmol) was added to the above solution. The resulting suspension was stirred at 135° C. for 20 h. The reaction mixture was cooled and diluted with EtOAc. The resulting solution was washed sequentially with aqueous ammonium chloride and aqueous LiCl (5%), dried over sodium sulfate and concentrated under reduced pressure. The resulting crude material was dissolved in DCM, treated with charcoal and purified by preparative TLC (DCM/MeOH 95:5) to afford the title compound (55.0 mg, 72%) as a brown yellow solid and as a mixture of rotamers: 1H NMR (500 MHz, CDCl3) δ 9.35 (d, J=1.5 Hz, 1H), 8.75 (d, J=8.0 Hz, 1H), 8.02-7.99 (m, 1H), 7.86 (d, J=8.5 Hz, 1H), 7.69 (d, J=8.5 Hz, 0.3H), 7.59 (d, J=8.5 Hz, 0.7H), 7.40 (s, 1H), 7.09-7.06 (m, 1H), 6.93 (d, J=7.0 Hz, 1H), 4.72 (s, 0.7H), 4.64 (s, 1.3H), 3.79-3.67 (m, 2H), 3.69 (s, 3H), 2.99-2.97 (m, 2H), 2.08-2.02 (m, 2H), 1.44 (s, 3.3H), 1.38 (s, 5.7H).

Provenance & Evidence