Practical Synthesis of N-{4-[(2-Methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin- 6(1H)-yl)carbonyl]phenyl}biphenyl-2-carboxamide Monohydrochloride: an Arginine Vasopressin Antagonis
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- 作者：Takashi Tsunoda ; Atsuki Yamazaki ; Hidenori Iwamoto ; and Shuichi Sakamoto
- 刊名：Organic Process Research & Development
- 出版年：2003
- 出版时间：November 2003
- 年：2003
- 卷：7
- 期：6
- 页码：883 - 887
- 全文大小：89K
- 年卷期：v.7,no.6(November 2003)
- ISSN：1520-586X
文摘
A novel, reliable, and cost-effective synthetic route to N-{4-[(2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl)carbonyl]phenyl}biphenyl-2-carboxamide monohydrochloride (1, YM087),a potent Arginine vasopressin antagonist, has been developed.Using moisture-controlled potassium carbonate, imidazoleformation from 
-bromoketone furnished imidazobenzazepine,avoiding potential oxazole-ring formation. Catalytic reductionof nitro imidazobenzazepine afforded the corresponding aminein high yields. Treatment of the imidazole-containing aminedirectly, with a carbonyl chloride, afforded the target amidecircumventing protection of the imidazole.
-bromoketone furnished imidazobenzazepine,avoiding potential oxazole-ring formation. Catalytic reductionof nitro imidazobenzazepine afforded the corresponding aminein high yields. Treatment of the imidazole-containing aminedirectly, with a carbonyl chloride, afforded the target amidecircumventing protection of the imidazole.