(2aR,4S)-4-Dipropylamino-1,2,2a,3,4,5-hexahydro-benzo[cd]indole-6-carbonitrile | 132557-17-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (2aR,4S)-4-Dipropylamino-1,2,2a,3,4,5-hexahydro-benzo[cd]indole-6-carbonitrile
• 英文别名: (2aR,4S)-6-cyano-4-(di-n-propylamino)-1,2,2a,3,4,5-hexahydrobenz[cd]indole；(2aR,4S)-4-(dipropylamino)-1,2,2a,3,4,5-hexahydrobenzo[cd]indole-6-carbonitrile
• CAS: 132557-17-6
• 化学式: C₁₈H₂₅N₃
• 分子量: 283.417
• InChiKey: XCALUCYILVSFSA-GJZGRUSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  39.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2aR,4S)-4-Dipropylamino-1,2,2a,3,4,5-hexahydro-benzo[cd]indole-6-carbonitrile 在 manganese(IV) oxide 、 PPA 作用下， 以 溶剂黄146 为溶剂， 生成 (4R)-4-(二丙基氨基)-1,3,4,5-四氢苯并[cd]吲哚-6-甲酰胺
  参考文献：
  名称：

  The synthesis of (+)- and (−)-1-benzoyl-1,2,2a,3,4,5-hexahydrobenz[cd]indol-4-amine, and preparation of LY228729.

  摘要：

  Racemic epoxide 5 was reacted with S-Phenylethylamine to afford diastereomers 6 and 7, from which amino alcohol 6 could be isolated directly. Aziridine formation and tandem-hydrogenolysis provided optically pure primary amine 2 (31% from racemic 4), which was further elaborated to LY228729 (15), an interesting 5HT1a receptor agonist.

  DOI：

  10.1016/s0040-4039(00)97303-9
• 作为产物：
  描述：

  (+) (2aR,4S)-1-benzoyl-6-iodo-4-(di-n-propylamino)-1,2,2a,3,4,5-hexahydrobenz[cd]indole 在 sodium hydroxide 、 四(三苯基膦)钯 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 3.5h， 生成 (2aR,4S)-4-Dipropylamino-1,2,2a,3,4,5-hexahydro-benzo[cd]indole-6-carbonitrile
  参考文献：
  名称：

  Application of Palladium(0)-Catalyzed Processes to the Synthesis of Oxazole-Containing Partial Ergot Alkaloids

  摘要：

  Syntheses of the potent 5-HT1A agonists 2 and 3 were accomplished in several steps from the 6-iodo partial ergoline alkaloid 8. Disparate tactics available for construction of differentially substituted oxazoles led to the development of new and general methodology critical to the efficient preparations of 2 and 3. A novel palladium(0)- and copper(I)-cocatalyzed cyanation reaction provided efficient access to the nitrile 10, a key intermediate in the synthesis of 2. A palladium(0)-catalyzed cross-coupling reaction of 16 with oxazol-2-ylzinc chloride formed the potent 6.HT1A agonist 3.

  DOI：

  10.1021/jo970374j

文献信息

• 6-substituted-hexahydrobenz[cd]indoles
  申请人：Eli Lilly and Company

  公开号：US05229410A1

  公开（公告）日：1993-07-20

  The present invention provides 4-amino-6-substituted-hexahydrobenz[cd]indoles which are useful in treating disease states which can be benefited by an alteration of 5-HT.sub.1A receptors.

  本发明提供了4-氨基-6-取代-六氢苯[cd]吲哚，这些化合物在治疗可以受到5-HT.sub.1A受体变化有益的疾病状态方面是有用的。
• Method for improving primary memory and/or learning
  申请人：Eli Lilly and Company

  公开号：US05292766A1

  公开（公告）日：1994-03-08

  A method for improving primary memory or learning in a mammal comprising administering a 5-hydroxytryptamine receptor agonist which is selective for the 5-hydroxytryptamine-1A receptor subtype, or a pharmaceutically acceptable salt thereof.

  一种提高哺乳动物的原始记忆或学习能力的方法，包括给予一种选择性作用于5-羟色胺-1A受体亚型的5-羟色胺受体激动剂或其药学上可接受的盐。
• 6-Substituted hexahydrobenz[cd]indoles
  申请人：ELI LILLY AND COMPANY

  公开号：EP0444854A2

  公开（公告）日：1991-09-04

  The present invention provides 4-amino-6-substituted-hexahydrobenz[cd]indoles which are useful in treating disease states which can be benefited by an alteration of function at 5- HT1A receptors.

  本发明提供的 4-氨基-6-取代-六氢苯并[cd]吲哚可用于治疗因 5- HT1A 受体功能改变而获益的疾病状态。
• 6-Substituted-hexahydrobenz (CD) indoles
  申请人：ELI LILLY AND COMPANY

  公开号：EP0471569A1

  公开（公告）日：1992-02-19

  The present invention provides 4-amino-6-substituted-hexahydrobenz[cd]indoles which are useful in treating disease states which can be benefited by an alteration of 5-HT1A receptors.

  本发明提供了 4-氨基-6-取代-六氢苯并[cd]吲哚，可用于治疗可通过改变 5-HT1A 受体而获益的疾病状态。
• Synthetic Studies toward the Partial Ergot Alkaloid LY228729, a Potent 5HT_1A Receptor Agonist
  作者：M. A. Carr、P. E. Creviston、D. R. Hutchison、J. H. Kennedy、V. V. Khau、T. J. Kress、M. R. Leanna、J. D. Marshall、M. J. Martinelli、B. C. Peterson、D. L. Varie、J. P. Wepsiec

  DOI：10.1021/jo971256z

  日期：1997.12.1

  Synthetic studies on LY228729 (3) afforded two innovative approaches for the construction of this class of partial ergoline 5HT(1a) receptor agonists. The first synthesis is based upon a diastereoselective epoxidation of racemic olefin 5, followed by ring opening and covalent resolution to furnish the key amino alcohol 8. Aziridination of amino alcohol 8, with subsequent tandem hydrogenolysis of the benzylic aziridine and auxiliary bonds, provided access to the optically active primary amine 13. A novel catalytic carboxamidation reaction installed the requisite side chain, Alternatively, the chiral pool was drawn upon for the single stereogenic center by virtue of L-tryptophan, albeit by a more circuitous route than expected. L-Tryptophan was differentially protected and reduced to the indoline diastereomers 26a,b which were separated by fractional crystallization. The two indoline diastereoisomers were independently cyclized by a Friedel-Crafts protocol, which under thermodynamic control afforded enantiomeric ketones 30a. The ketone was deoxygenated with a two-step reduction protocol to intersect the initial route and complete the second total synthesis. The two routes offer complementary access to this exciting class of partial ergot alkaloids.