Cl.[C:2]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:18][CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[CH:8][CH:7]=1)([CH3:5])([CH3:4])[CH3:3].C[O:20][C:21](=[O:26])[CH2:22][CH2:23][CH2:24]Br.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[OH-].[Li+:36]>C(#N)C.O>[Li+:36].[C:2]([C:6]1[CH:7]=[CH:8][C:9]([N:12]2[CH2:18][CH2:17][CH2:16][N:15]([CH2:24][CH2:23][CH2:22][C:21]([O-:26])=[O:20])[CH2:14][CH2:13]2)=[CH:10][CH:11]=1)([CH3:5])([CH3:3])[CH3:4]A mixture of 1-(4-tert-butyl-phenyl)-[1,4]diazepane hydrochloride (220 mg; 0.82 mmol, prepared in accordance with Example 161), 4-bromo-butyric acid methyl ester (160 mg; 0.82 mmol), potassium carbonate (113 mg; 0.82 mmol) and potassium iodide (136 mg; 0.82 mmol) in acetonitrile (5 mL) is heated to 100° C. for 3 hours. The reaction mixture is allowed to attain room temperature and filtered. The filtrate is diluted with a solution of lithium hydroxide (59 mg; 2.46 mmol) in water (2 mL) and the resulting mixture is stirred at room temperature over night. All volatiles are then removed under high vacuum and more lithium hydroxide solution is added to drive the reaction to completion. Acetonitrile is added and the precipitate formed is then filtered and dried under high vacuum to afford the desired product (514 mg) which is used in the next step without further purification.
불러오는 중…
