1-[2-((4aR,11R,11aS)-11-methyl-9-trifluoromethyl-2,3,4,4a,5,6,11,11a-octahydropyrido[4,3-b]carbazol-2-yl)ethyl]cyclohexanecarboxylic acid benzenesulfonic acid salt | 1001438-96-5

• 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-[2-((4aR,11R,11aS)-11-methyl-9-trifluoromethyl-2,3,4,4a,5,6,11,11a-octahydropyrido[4,3-b]carbazol-2-yl)ethyl]cyclohexanecarboxylic acid benzenesulfonic acid salt
• 英文别名: Amg-076；1-[2-[(4aR,11R,11aS)-11-methyl-9-(trifluoromethyl)-1,3,4,4a,5,6,11,11a-octahydropyrido[4,3-b]carbazol-2-yl]ethyl]cyclohexane-1-carboxylic acid;benzenesulfonic acid
• CAS: 1001438-96-5
• 化学式: C₆H₆O₃S*C₂₆H₃₃F₃N₂O₂
• 分子量: 620.733
• InChiKey: IBDOVKSLMMFQPJ-IUPOGUASSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.14
• 重原子数：
  43
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  1-[2-((4aR,11R,11aS)-11-methyl-9-trifluoromethyl-2,3,4,4a,5,6,11,11a-octahydropyrido[4,3-b]carbazol-2-yl)ethyl]cyclohexanecarboxylic acid tert-butyl ester benzenesulfonic acid salt 在 苯磺酸 作用下， 以 乙腈 为溶剂， 反应 5.5h， 以81%的产率得到1-[2-((4aR,11R,11aS)-11-methyl-9-trifluoromethyl-2,3,4,4a,5,6,11,11a-octahydropyrido[4,3-b]carbazol-2-yl)ethyl]cyclohexanecarboxylic acid benzenesulfonic acid salt
  参考文献：
  名称：

  Stereoselective Synthesis of a MCHr1 Antagonist

  摘要：

  [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.

  DOI：

  10.1021/jo701894v

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.