Potassium Carbonate → HCID 67514630, compound

Participants

Reaction Steps

2-Methylpropyl 6-[4-(chlorocarbonyl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-benzimidazole-1-carboxylate (150 mg, 0.38 mmol) and 2-(3-fluoro-4-methylphenyl)piperidine (reagent preparation 1) (80 mg, 0.41 mmol) were taken into THF (3.5 mL) followed by addition of diisopropylethylamine (0.33 mL, 1.9 mmol) and the resulting solution was heated to reflux for 3 h. The mixture was then cooled to room temperature and partitioned with ethyl acetate and 20% aqueous citric acid. The organic phase was separated, dried over sodium sulfate then filtered and concentrated. The residue obtained was taken up into methanol (5 mL) followed by addition of solid potassium carbonate (518 mg, 3.75 mmol) and the mixture was stirred for 12 h at room temperature. The mixture was then concentrated and the residue taken into a minimum of aqueous acetonitrile and purified by preparative reverse phase HPLC. Lyophillization of the combined pure fraction afforded 4-{[2-(3-fluoro-4-methylphenyl)piperidin-1-yl]carbonyl}-7-(2-methyl-1H-benzimidazol-6-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine (23 mg) as an amorphous solid. 1H NMR (400 MHz, d6-DMSO): 12.18 (br s, 1H), 7.59 (br s, 1H), 7.47 (dd, 2H), 7.40 (d, 1H), 7.27 (dd, 1H), 7.12 (t, 1H), 7.01 (d, 1H), 6.96 (d, 2H), 4.59 (m, 1H), 4.40 (dd, 2H), 4.18 (m, 2H), 3.53 (m, 2H), 3.21 (m, 1H), 3.00 (m, 1H), 2.50 (s, 3H), 2.24 (s, 3H), 1.96 (m, 1H), 1.79 (m, 1H), 1.62-1.38 (m, 4H). MS (EI) for C30H31FN4O2: 499 (MH+).

Provenance & Evidence