(+)-1-Benzoyl-1,2,2a,3,4,5-hexahydrobenzindol-4-amine | 132619-29-5

• 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: (+)-1-Benzoyl-1,2,2a,3,4,5-hexahydrobenzindol-4-amine
• 英文别名: (2aR,4S)-1-Benzoyl-4-amino-1,2,2a,3,4,5-hexahydrobenz[cd]indole；[(2aR,4S)-4-amino-2a,3,4,5-tetrahydro-2H-benzo[cd]indol-1-yl]-phenylmethanone
• CAS: 132619-29-5
• 化学式: C₁₈H₁₈N₂O
• 分子量: 278.354
• InChiKey: ZBQKMEILFXHNME-LSDHHAIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  46.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+)-1-Benzoyl-1,2,2a,3,4,5-hexahydrobenzindol-4-amine 在 manganese(IV) oxide 、 正丁基锂 、 溴 、 sodium acetate 、 potassium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 溶剂黄146 、 乙腈 为溶剂， 反应 10.0h， 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：

  (S)-3-(1-Benzoyl-2,3-dihydro-1H-indol-3-yl)-2-(2,2,2-trifluoro-acetylamino)-propionyl chloride 在 palladium on activated charcoal sodium hydroxide 、 sodium tetrahydroborate 、 三氯化铝 、 氢气 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， -10.0~25.0 ℃ 、310.27 kPa 条件下， 反应 48.0h， 生成 (+)-1-Benzoyl-1,2,2a,3,4,5-hexahydrobenzindol-4-amine
  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

• Amesergide and structurally related nor-D-ergolines: 5HT2 receptor interactions in the rat
  作者：Michael J. Martinelli、William Bloomquist、Barry C. Peterson、Marlene L. Cohen

  DOI：10.1021/jm00070a011

  日期：1993.9

  amesergide inhibited the pressor response to serotonin in doses of 0.01-0.1 mg/kg i.v. The homochiral isopropyl tricyclic ergoline was more potent as a 5HT2 receptor antagonist than the epimeric (unnatural stereochemistry) analogue. Thus, the isopropyl moiety on the indole nitrogen is important for vascular 5HT2 receptor affinity in the rat. Most importantly, these data suggest that conformational rigidity

  通过高度收敛的对映体特异性策略合成了一系列三环（nor-D）部分麦角灵，最终由外消旋三环酮产生。将迈克尔加成丙烯酰胺，然后进行还原性甲基化，得到了关键中间体。选择性脱保护和氧化提供了三环麦角灵。与麦角灵母本麦角胺相比，部分麦角灵的血管5HT2受体相互作用显着降低，这是通过在成髓大鼠中通过激活加压反应或阻断5HT诱导的加压反应而在体内确定的。去异丙基三环麦角灵具有适度的升压活性，这不太可能与5HT2受体活化有关，因为这些化合物不会抑制对5-羟色胺的升压反应。相反，异丙基三环麦角灵没有激动剂活性，但在1 mg / kg静脉注射时抑制了对5-羟色胺的升压反应。iv。麦角灵碱在0.01-0.1 mg / kg剂量下抑制了对5-羟色胺的升压反应。 5HT2受体拮抗剂而不是差向异构体（非自然立体化学）类似物。因此，吲哚氮上的异丙基部分对于大鼠中血管5HT2受体的亲和力很重要。最重要的是，这些数据表明麦
• Preparation of 1-benzoyl-4-(amino)-1,2,2a,3,4,5-hexahydrobenz[CD]indoles from L-tryptophan
  作者：David L. Varie

  DOI：10.1016/s0040-4039(00)97304-0

  日期：1990.1

  Acid6a, derived from L-tryptophan, has been shown to be a useful precursor to partial ergot structures such as3. Optically pure amine(+)−13, a key intermediate in the synthesis of3, was prepared in 45% overall yield from6a via a four step sequence employing an intramolecular Friedel-Crafts cyclization and a C-5 deoxygenation procedure.

  衍生自L-色氨酸的酸6a已被证明是部分麦角结构（如3）的有用前体。通过分子内的Friedel-Crafts环化和C-5脱氧程序，通过四个步骤，以6a的总收率从4a制备了光学纯胺（+）-13（3的合成关键中间体）。
• 6-substituted-hexahydrobenz [CD] indoles
  申请人：Eli Lilly and Company

  公开号：US05470853A1

  公开（公告）日：1995-11-28

  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.1.sbsb.A receptors.

  本发明提供了4-氨基-6-取代-六氢苯并[cd]吲哚，可用于治疗可以通过改变5-HT.sub.1.sbsb.A受体而受益的疾病状态。
• 6-substituted-hexahydrobenz[cd]indoles
  申请人：Eli Lilly and Company

  公开号：US05302612A1

  公开（公告）日：1994-04-12

  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，可用于治疗通过改变5-HT.sub.1A受体可以获益的疾病状态。
• 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。