反应详情

2-Methylpropyl 2-(4-{4-[(4-cyanopiperidin-1-yl)carbonyl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}phenyl)-1H-imidazole-1-carboxylate (296 mg, 0.56 mmol) was taken into methanol (10 mL), THF (2 mL) and water (0.5 mL) then warmed to give a homogeneous solution. Potassium carbonate (160 mg, 1.15 mmol) and the mixture was stirred for 30 minutes. The mixture was then concentrated and partitioned with ethyl acetate and 10% aqueous citric acid. The organic solution was washed with brine, dried over anhydrous sodium sulfate then filtered and concentrated. The residue was purified by silica gel chromatography (10% ethanol in ethyl acetate) to give 1-({7-[4-(1H-imidazol-2-yl)phenyl]-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl}carbonyl)piperidine-4-carbonitrile (155 mg, 65% yield). 1H NMR (400 MHz, d4-methanol): 7.92 (d, 2H), 7.69 (d, 2H), 7.56 (d, 1H), 7.51 (dd, 1H), 7.15 (s, 2H), 7.04 (d, 1H), 4.51 (s, 2H), 4.21 (tr, 2H), 3.70 (tr, 2H), 3.49-3.43 (m, 2H), 3.13 (m, 2H), 2.97 (m, 1H), 1.98-1.93 (m, 2H), 1.86-1.78 (m, 2H). MS (EI) for C25H25N5O2: 429 (MH+).

1. temperaturethen warmed
2. customto give a homogeneous solution
3. concentrationThe mixture was then concentrated
4. custompartitioned with ethyl acetate and 10% aqueous citric acid
5. washThe organic solution was washed with brine
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationthen filtered
8. concentrationconcentrated
9. customThe residue was purified by silica gel chromatography (10% ethanol in ethyl acetate)