Azabicyclo chemistry. I. Synthesis of 1,5-methano-7-methoxy-2,3,4,5-tetrahydro-1H-2-benzazepines. B-norbenzomorphans.
Azabicyclo chemistry. I. Synthesis of 1,5-methano-7-methoxy-2,3,4,5-tetrahydro-1H-2-benzazepines. B-norbenzomorphans.
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氮杂双环化学。
DOI：
10.1021/jm00295a002
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发表时间：
1970
影响因子：
7.3
通讯作者：
M. Mokotoff
中科院分区：
文献类型：
--
作者：
A. Jacobson;M. Mokotoff
结论。1，5-亚甲基四氢-2-苯并-氮杂卓是具有药理活性的化合物，比可比较的6，7-苯并吗啉更具有药理活性。因此，从6，7-苯并吗啡烷到B-去甲苯并吗啡烷分子的相当大的空间变化可以增强抗癫痫活性，并由此推断，药物-受体相互作用，即使B-去甲苯并吗啡烷既缺乏“中心”碳原子又缺乏游离的苄基，前者出现在几乎所有已知的具有吗啡样活性的抗癫痫药中。11的依赖性测定和各种X-的7-羟基类似物的合成。（5）8在多聚磷酸、三氟乙酸酐或N-乙基-5-苯基异恶唑鎓 3 ′-磺酸盐中的缩合反应（见R. B。Woodward，R. A. Olofson和H. Mayer，Tetrahedron，Suppl.，8，321（1966））给出很少或没有内酰胺。在密封管中在不同温度下加热7或8（作为碱），内酰胺产率很低。(6)深圳市爱德瑞化学有限公司威斯康星州密尔沃基(7)二环己基碳二亚胺在各种溶剂（CH 2Cl 2、THF、CHCl 4等）中的溶液也是令人满意的缩合8。证明吡啶是最好的介质，避免了添加叔碱EtsN。不幸的是，反应中的副产物二环己基脲极难与9分离。
Conclusion.—The l, 5-methanotetrahydro-2-benz-azepines are analgetically active compounds, more so than the comparable 6, 7-benzomorphans. Thus, the considerable steric change from the 6, 7-benzomorphans to the B-norbenzomorphan molecule may enhance analgetic activity and by inference, drug-receptor interaction, even though the B-norbenzomorphans lack both a “central” carbon atom and a free benzylic group, the former occurring in almost all of the known analgetics which have morphine-like activity. The determination of the dependence liability of 11 and the synthesis of 7-hydroxy analogs of various X-(5) Attempted condensation of 8 in polyphosphoric acid, trifluoroacetic anhydride, or with N-ethyl-5-phenylisoxazoIium 3'-sulfonate6 (see R. B." Woodward, R. A. Olofson, and H. Mayer, Tetrahedron, Suppl., 8, 321 (1966)) gave little or no lactam. Heating of 7 or 8 (as the base) in a sealed tube at various temperatures gave poor yields of lactam.(6) Aldrich Chemical Co., Milwaukee, Wis.(7) Dicyclohexylcarbodiimide in various solvents (CH2CI2, THF, CHCU; etc.) was also satisfactory for the condensation of 8. Pyridine proved to be the best medium, obviating the addition of a tertiary base, EtsN. Un-fortunately, dicyclohexylurea, the coproduct in the reaction, was extremely difficult to separate from 9.