(4aR,8S,8aR)-8-methyl-6-oxo-octahydroisoquinoline-2-carboxylic acid tert-butyl ester | 693823-70-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: (4aR,8S,8aR)-8-methyl-6-oxo-octahydroisoquinoline-2-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl (4aR,8S,8aR)-8-methyl-6-oxooctahydroisoquinoline-2(1H)-carboxylate；tert-butyl (4aR,8S,8aR)-8-methyl-6-oxo-1,3,4,4a,5,7,8,8a-octahydroisoquinoline-2-carboxylate
• CAS: 693823-70-0
• 化学式: C₁₅H₂₅NO₃
• 分子量: 267.368
• InChiKey: HCTPECNDUHDFCH-DMDPSCGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4aR,8S,8aR)-8-methyl-6-oxo-octahydroisoquinoline-2-carboxylic acid tert-butyl ester 、 4-(三氟甲基)苯肼 在 硫酸 、 sodium hydroxide 作用下， 以 丙醇 为溶剂， 反应 1.75h， 生成 (4aR,11R,11aS)-11-methyl-9-(trifluoromethyl)-2,3,4,4a,5,6,11,11a-octahydro-1H-pyrido[4,3-b]carbazole
  参考文献：
  名称：

  [EN] FUSED HETEROCYCLIC COMPOUNDS
  [FR] COMPOSES HETEROCYCLIQUES CONDENSES

  摘要：

  提供了一种在治疗和/或预防由G蛋白偶联受体介导的疾病或紊乱方面有用的化合物、组合物和方法。特别是，本发明的化合物在治疗和/或预防进食紊乱、肥胖、焦虑症和情绪障碍方面是有用的。

  公开号：

  WO2004043958A1
• 作为产物：
  描述：

  ((7S,8R,9S)-7-methyl-9-vinyl-1,4-dioxaspiro[4.5]decan-8-yl)methanol 在 N-碘代丁二酰亚胺 、 四丙基高钌酸铵 、 偶氮二异丁腈 、 氢气 、 三正丁基氢锡 、 palladium(II) hydroxide 、 potassium carbonate 、 对甲苯磺酸 、 N-甲基吗啉氧化物 作用下， 以 甲醇 、 二氯甲烷 、 环己烷 、 水 、 乙酸乙酯 、 丙酮 、 苯 为溶剂， 20.0 ℃ 、506.66 kPa 条件下， 反应 34.5h， 生成 (4aR,8S,8aR)-8-methyl-6-oxo-octahydroisoquinoline-2-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Catalytic and Enantioselective Synthesis of a Key Intermediate of the MCHr1 Antagonist AMG 076

  摘要：

  A chiral decahydroisoquinoline was constructed using our asymmetric Diels-Alder reaction catalyzed by a chiral Yb (ytterbium) complex as a key step. The decahydroisoquinoline is a synthetic intermediate of the anti-obesity drug candidate AMG 076 (Amgen).

  DOI：

  10.3987/com-14-s(k)64

文献信息

• Stereoselective Synthesis of a MCHr1 Antagonist
  作者：Denise Andersen、Thomas Storz、Pingli Liu、Xin Wang、Leping Li、Pingchen Fan、Xiaoqi Chen、Alan Allgeier、Alain Burgos、Jason Tedrow、Jean Baum、Ying Chen、Rich Crockett、Liang Huang、Rashid Syed、Robert D. Larsen、Mike Martinelli

  DOI：10.1021/jo701894v

  日期：2007.12.1

  [GRAPHICS]Melanin-concentrating hormone (MCH) is implicated in the feeding behavior in mammals affording a potential target to control overeating in people. Compound 1 (AMG 076) has been identified as a potent MCHr1 antagonist for the treatment of obesity. A synthesis suitable for the large-scale preparation of this lead candidate was developed to support preclinical studies. A Robinson annulation of benzylpiperidone and resolution of the desired enone from a mixture of the diastereomers afforded key intermediate 6 after a stereoselective hydrogenation. Subsequent Fischer indole synthesis with hydrazine 5 then provided the advanced intermediate, indole 2. Two complementary reductive amination strategies employing either aldehyde 3 or lactol 4 led to the synthesis of title compound 1.
• Fused heterocyclic compounds
  申请人：Chen Xi

  公开号：US20080058365A1

  公开（公告）日：2008-03-06

  Compounds, compositions and methods are provided that are useful in the treatment and/or prevention of a condition or disorder mediated by a G-protein coupled receptor. In particular, the compounds of the invention are useful in the treatment and/or prevention of eating disorders, obesity, anxiety disorders and mood disorders.
• [EN] FUSED HETEROCYCLIC COMPOUNDS<br/>[FR] COMPOSES HETEROCYCLIQUES CONDENSES
  申请人：TULARIK INC

  公开号：WO2004043958A1

  公开（公告）日：2004-05-27

  Compounds, compositions and methods are provided that are useful in the treatment and/or prevention of a condition or disorder mediated by a G-protein coupled receptor. In particular, the compounds of the invention are useful in the treatment and/or prevention of eating disorders, obesity, anxiety disorders and mood disorders.

  提供了一种在治疗和/或预防由G蛋白偶联受体介导的疾病或紊乱方面有用的化合物、组合物和方法。特别是，本发明的化合物在治疗和/或预防进食紊乱、肥胖、焦虑症和情绪障碍方面是有用的。
• Catalytic and Enantioselective Synthesis of a Key Intermediate of the MCHr1 Antagonist AMG 076
  作者：Atsushi Nishida、Shinji Harada、Haruka Ishii、Daisuke Shirasaki

  DOI：10.3987/com-14-s(k)64

  日期：——

  A chiral decahydroisoquinoline was constructed using our asymmetric Diels-Alder reaction catalyzed by a chiral Yb (ytterbium) complex as a key step. The decahydroisoquinoline is a synthetic intermediate of the anti-obesity drug candidate AMG 076 (Amgen).