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温度

0 °C

2-methylpropyl 2-[4-(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)phenyl]-1H-imidazole-1-carboxylate (361 mg, 0.92 mmol) was taken into dichloromethane (5 mL) followed by addition of DIPEA (0.32 mL, 1.84 mmol). The solution thus obtained was added slowly by syringe over several minutes to a solution of phosgene (20 W % in toluene, 0.49 mL, 0.93 mmol) diluted in dichloromethane (5 mL) and cooled to 0° C. The resulting mixture was stirred for 5 minutes then allowed to warm to room temperature and concentrated. The residue was taken back into dichloromethane (5 mL) followed by addition of DIPEA (0.48 mL, 2.76 mmol) and 4-cyanopiperidine hydrochloride salt (156 mg, 1.06 mmol) then stirred for 12 h. The mixture was concentrated then 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 (100% ethyl acetate) to give 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, 61% yield) as a crystalline solid. MS (EI) for C30H33N5O4: 529 (MH+).

1. customThe solution thus obtained
2. temperatureto warm to room temperature
3. concentrationconcentrated
4. stirringthen stirred for 12 h
5. concentrationThe mixture was concentrated
6. customthen partitioned with ethyl acetate and 10% aqueous citric acid
7. washThe organic solution was washed with brine
8. dry with materialdried over anhydrous sodium sulfate
9. filtrationthen filtered
10. concentrationconcentrated
11. customThe residue was purified by silica gel chromatography (100% ethyl acetate)