(+)-(2aR,4S)-1-benzoyl-4-(dipropylamino)-1,2,2α,3,4,5-hexahydrobenz-[cd]-indole-6-carbonitrile | 132557-16-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (+)-(2aR,4S)-1-benzoyl-4-(dipropylamino)-1,2,2α,3,4,5-hexahydrobenz-[cd]-indole-6-carbonitrile
• 英文别名: (-) (2aR,4s)-1-Benzoyl-6-cyano-4-(di-n-propylamino)-1,2,2a,3,4,5-hexahydrobenz[cd]indole；(2aR,4S)-1-benzoyl-4-(dipropylamino)-2a,3,4,5-tetrahydro-2H-benzo[cd]indole-6-carbonitrile
• CAS: 132557-16-5
• 化学式: C₂₅H₂₉N₃O
• 分子量: 387.525
• InChiKey: HCUPXVOUDNDEBD-SFTDATJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  47.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+)-(2aR,4S)-1-benzoyl-4-(dipropylamino)-1,2,2α,3,4,5-hexahydrobenz-[cd]-indole-6-carbonitrile 在 manganese(IV) oxide 、 正丁基锂 作用下， 以 四氢呋喃 、 二氯甲烷 、 溶剂黄146 为溶剂， 反应 7.5h， 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：

  Synthetic Studies toward the Partial Ergot Alkaloid LY228729, a Potent 5HT_1A Receptor Agonist

  摘要：

  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.

  DOI：

  10.1021/jo971256z
• 作为产物：
  描述：

  ((2aR,4S)-4-Amino-6-bromo-2a,3,4,5-tetrahydro-2H-benzo[cd]indol-1-yl)-phenyl-methanone 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 2.5h， 生成 (+)-(2aR,4S)-1-benzoyl-4-(dipropylamino)-1,2,2α,3,4,5-hexahydrobenz-[cd]-indole-6-carbonitrile
  参考文献：
  名称：

  Synthetic Studies toward the Partial Ergot Alkaloid LY228729, a Potent 5HT_1A Receptor Agonist

  摘要：

  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.

  DOI：

  10.1021/jo971256z

文献信息

• The synthesis of carbon-14 labeled (R)-4-(dipropylamino)-1,3,4,5-tetrahydrobenz[cd]indole-6-carboxamide hippurate. A partial ergoline with 5-HT1A agonist activity and an125I-labeled analog
  作者：William J. Wheeler、Steven P. Swanson、David L. Varie、Douglas D. O'Bannon

  DOI：10.1002/jlcr.907

  日期：2005.2

  Partial ergoline agonists such as (R)-4-(dipropylamino)-1,3,4,5-tetrahydrobenz[cd]-indole-6-carboxamide (LY228729, 1a) mimic a locked conformational analog of serotonin and in fact possess potent in vitro activity as agonists of the 5-HT1A receptor. In the course of pre-clinical investigation of 1a for potential use as an anxiolytic agent, 1b was prepared in a five step synthesis from K14CN. In addition

  部分麦角碱激动剂，如 (R)-4-(二丙氨基)-1,3,4,5-四氢苯并[cd]-吲哚-6-甲酰胺 (LY228729, 1a) 模拟血清素的锁定构象类似物，实际上具有有效的作为 5-HT1A 受体激动剂的体外活性。在 1a 潜在用作抗焦虑剂的临床前研究过程中，1b 是通过 K14CN 的五步合成制备的。此外，还制备了 1a 的 125I 类似物，以帮助开发放射免疫分析 (RIA)。版权所有 © 2005 John Wiley & Sons, Ltd.
• 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。
• 6-Heterocyclic-4-amino-1,3,4,5-tetrahydrobenz[cd]indoles
  申请人：ELI LILLY AND COMPANY

  公开号：EP0506363A1

  公开（公告）日：1992-09-30

  6-heterocyclic-4-amino-1,3,4,5-tetrahydrobenz[cd]indoles are provided which are useful in modifying the function of serotonin in mammals.

  本研究提供了 6-杂环-4-氨基-1,3,4,5-四氢苯并[cd]吲哚，可用于改变哺乳动物体内血清素的功能。
• 6-Heterocyclic-4-amino-1,2,2a,3,4,5-hexahydrobenz[CD]indoles
  申请人：ELI LILLY AND COMPANY

  公开号：EP0506369A1

  公开（公告）日：1992-09-30

  6-Heterocyclic-4-amino-1,2,2a,3,4,5-hexahydrobenz-[cd]indoles are provided which are useful in modifying the function of serotonin in mammals.

  本研究提供了 6-杂环-4-氨基-1,2,2a,3,4,5-六氢苯并-[cd]吲哚，可用于改变哺乳动物体内血清素的功能。