[CH:1]1([NH2:4])[CH2:3][CH2:2]1.[Cl:5][C:6]1[N:7]=[C:8]([C:13]([NH:15][CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][C:17]2=O)=[O:14])[NH:9][C:10]=1[CH2:11][CH3:12].C([BH3-])#N.[Na+].C(O)(=O)C>O1CCCC1>[Cl:5][C:6]1[N:7]=[C:8]([C:13]([NH:15][C@@H:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:26])([CH3:28])[CH3:27])=[O:23])[CH2:18][C@H:17]2[NH:4][CH:1]2[CH2:3][CH2:2]2)=[O:14])[NH:9][C:10]=1[CH2:11][CH3:12]Cyclopropylamine (249 μL, 3.59 mmol) was added to a solution of tert-butyl 4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-oxopiperidine-1-carboxylate obtained in Example (201c) (190 mg, 0.512 mmol) in tetrahydrofuran (6 mL), and the mixture was heated under reflux at 50° C. for four hours. The reaction solution was concentrated under reduced pressure, and then tetrahydrofuran (3 mL) and methanol (3 mL) were added. Cyclopropylamine (71.0 μL, 0.102 mmol), sodium cyanoborohydride (97.0 mg, 1.54 mmol) and acetic acid (293 μL, 5.12 mmol) were added, and the mixture was stirred at room temperature for 15 hours. The reaction solution was concentrated under reduced pressure. Saturated aqueous sodium bicarbonate solution was added to the residue, followed by extraction with ethyl acetate. The resulting organic layer was washed with brine, and dried over anhydrous sodium sulfate, and then the insoluble matter was separated by filtration. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography and preparative TLC (eluent: chloroform:methanol=10:1 v/v) to obtain 34 mg of the cis isomer of the title compound (16%) as a pale yellow oily substance and 32 mg of the trans isomer of the title compound (15%) as a pale yellow oily substance.
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