(+) (2aR,4S)-1-benzoyl-6-iodo-4-(di-n-propylamino)-1,2,2a,3,4,5-hexahydrobenz[cd]indole | 133256-91-4

• 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-6-iodo-4-(di-n-propylamino)-1,2,2a,3,4,5-hexahydrobenz[cd]indole
• 英文别名: (+)(2aR,4S)-l-benzoyl-6-iodo-4-(di-n-propylamino)-1,2,2a,3,4,5-hexahydrobenz[cd]indole；[(2aR,4S)-4-(dipropylamino)-6-iodo-2a,3,4,5-tetrahydro-2H-benzo[cd]indol-1-yl]-phenylmethanone
• CAS: 133256-91-4
• 化学式: C₂₄H₂₉IN₂O
• 分子量: 488.412
• InChiKey: DDABWWKWYOBDGN-OALUTQOASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+) (2aR,4S)-1-benzoyl-6-iodo-4-(di-n-propylamino)-1,2,2a,3,4,5-hexahydrobenz[cd]indole 在 manganese(IV) oxide 、 sodium hydroxide 、 氨 、 钯 、 三苯基膦 作用下， 以 乙醇 、 二氯甲烷 、 水 、 溶剂黄146 、 甲苯 为溶剂， 反应 23.5h， 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：

  在 palladium on activated charcoal sodium hydroxide 、 sodium tetrahydroborate 、 三氯化铝 、 氢气 、 碘 、 potassium carbonate 、 过碘酸 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 、 乙腈 为溶剂， -10.0~75.0 ℃ 、310.27 kPa 条件下， 反应 66.0h， 生成 (+) (2aR,4S)-1-benzoyl-6-iodo-4-(di-n-propylamino)-1,2,2a,3,4,5-hexahydrobenz[cd]indole
  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

• 6-heterocyclic-4-amino-1,2,2a,3,4,5-hexahydrobenz[cd]indoles
  申请人：Eli Lilly and Company

  公开号：US05347013A1

  公开（公告）日：1994-09-13

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

  提供了6-杂环-4-氨基-1,2,2a,3,4,5-六氢苯并[cd]吲哚，这些化合物在改变哺乳动物中的5-羟色胺功能方面很有用。
• 6-heterocyclic-4-amino-1,3,4,5-tetrahydrobenz[CD]indoles
  申请人：Eli Lilly and Company

  公开号：US05594019A1

  公开（公告）日：1997-01-14

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

  提供了6-杂环-4-氨基-1,3,4,5-四氢苯[cd]吲哚，它们在改变哺乳动物中的血清素功能方面是有用的。
• 6-heterocyclic-4-amino-1,2,2a,3,4,5-hexahydrobenz[CD]indoles
  申请人：Eli Lilly and Company

  公开号：US05648356A1

  公开（公告）日：1997-07-15

  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.

  提供了6-杂环-4-氨基-1,2,2a,3,4,5-六氢苯[cd]吲哚，它们对于改变哺乳动物中的血清素功能是有用的。
• 6-heterocyclic-4-amino-1,3,4,5-tetrahydrobenz[cd]indoles
  申请人：Eli Lilly and Company

  公开号：US05624944A1

  公开（公告）日：1997-04-29

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

  提供了6-杂环-4-氨基-1,3,4,5-四氢苯[cd]吲哚，可用于修改哺乳动物中的血清素功能。
• 6-heterocyclic-4-amino-1,2,2A,3,4,5-hexahydrobenz [CD] indoles
  申请人：ELi Lilly and Company

  公开号：US05627199A1

  公开（公告）日：1997-05-06

  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.

  提供了6-杂环-4-氨基-1,2,2a,3,4,5-六氢苯[cd]吲哚，可用于修饰哺乳动物中的5-羟色胺功能。