[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]2[CH:10]([CH:11]2[C:14]([OH:16])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:17]1C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C.C(N(C(C)C)CC)(C)C.N>C(Cl)Cl.CO>[C:14]([CH:11]1[CH:12]2[CH:10]1[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:13]2)(=[O:16])[NH2:17]The 3-(tert-butoxycarbonyl)-3-azabicyclo[3.1.0]hexane-6-carboxylic acid (252 mg, 1.11 mmol) prepared in Example 3, benzotriazole (180 mg, 1.33 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (255 mg, 1.33 mmol) were dissolved in 3.0 mL of methylene chloride and diisopropylethylamine (232 μL, 1.33 mmol) was added dropwise. After adding 2 M ammonia solution (2.49 mL, 4.98 mmol) dissolved in methanol dropwise at 0° C., the mixture was stirred at room temperature for 4 hours. The completion of the reaction was confirmed by TLC (CH2Cl2:MeOH=15:1). After the reaction was completed, the reaction mixture was diluted with methylene chloride and washed with saturated sodium chloride. The organic layer was dried with anhydrous magnesium sulfate, filtered, concentrated under reduced pressure and separated by column chromatography (CH2Cl2:MeOH=15:1) to obtain 177 mg (70.6%) of the target compound.
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