4-[3-methoxycarbonyl-2-(1',2',3',4'-tetrahydroquinolin-3'-yl)propyl]piperidine-1-carboxylic acid tert-butyl ester | 1149754-11-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-[3-methoxycarbonyl-2-(1',2',3',4'-tetrahydroquinolin-3'-yl)propyl]piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 4-[(2S)-4-methoxy-4-oxo-2-(1,2,3,4-tetrahydroquinolin-3-yl)butyl]piperidine-1-carboxylate
• CAS: 1149754-11-9
• 化学式: C₂₄H₃₆N₂O₄
• 分子量: 416.561
• InChiKey: LNYREZFRWFJOJC-XJDOXCRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (S)-4-(3-methoxycarbonyl-2-quinolin-3-yl-propyl)piperidine-1-carboxylic acid tert-butyl ester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 水 为溶剂， 反应 28.0h， 以70%的产率得到4-[3-methoxycarbonyl-2-(1',2',3',4'-tetrahydroquinolin-3'-yl)propyl]piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Suzuki−Miyaura Approach to JNJ-26076713, an Orally Active Tetrahydroquinoline-Containing α_Vβ₃/α_Vβ₅ Integrin Antagonist. Enantioselective Synthesis and Stereochemical Studies

  摘要：

  An improved scale-up synthesis was required for the alpha(V)beta(3)/alpha(V)beta(5) integrin antagonist 1, which had demonstrated oral efficacy in eye disease models of angiogenesis and vascular permeability. A stereodefined, quinoline-substituted, unsaturated ester was conveniently prepared by a Suzuki-Miyaura coupling to facilitate exploration of multiple methods of asymmetric reduction. The catalytic chiral hydrogenation of the corresponding unsaturated acid (Z-5b) with a ruthenium-based metal precursor and the (R)-XylPhanePhos ligand proved particularly efficient and economical. The resulting (3S)-quinoline-containing intermediate was reduced to an equal mixture of tetrahydroquinoline diastereomers. The undesired diastereomer could be recycled to the desired one by an oxidation/reduction protocol. The absolute stereochemistry of 1 was established as 3S,3'S by a combination of X-ray diffraction and chemical means.

  DOI：

  10.1021/jo702551t

文献信息

• Enantioselective process for preparing a substituted alkanoic acid
  申请人：Kinney William A.

  公开号：US20090124804A1

  公开（公告）日：2009-05-14

  The present invention is directed to a process for enantioselectively preparing substituted piperidine alkanoic acid integrin antagonist compounds.

  本发明涉及一种用于对手性选择性地制备替代哌啶烷基酸整合素拮抗剂化合物的方法。
• [EN] ENANTIOSELECTIVE PROCESS FOR PREPARING A SUBSTITUTED ALKANOIC ACID<br/>[FR] PROCÉDÉ ÉNANTIOSÉLECTIF POUR PRÉPARER UN ACIDE ALCANOÏQUE SUBSTITUÉ
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2009058314A1

  公开（公告）日：2009-05-07

  The present invention is directed to a process for enantioselectively preparing substituted piperidine alkanoic acid integrin antagonist compounds.

  本发明涉及一种手性选择性制备取代哌啶烷基酸整合素拮抗剂化合物的方法。
• US8680278B2
  申请人：——

  公开号：US8680278B2

  公开（公告）日：2014-03-25
• Suzuki−Miyaura Approach to JNJ-26076713, an Orally Active Tetrahydroquinoline-Containing α_Vβ₃/α_Vβ₅ Integrin Antagonist. Enantioselective Synthesis and Stereochemical Studies
  作者：William A. Kinney、Christopher A. Teleha、Andrew S. Thompson、Maria Newport、Ryan Hansen、Scott Ballentine、Shyamali Ghosh、Andrew Mahan、Gabriela Grasa、Antonio Zanotti-Gerosa、Jules Dingenen、Carsten Schubert、Yong Zhou、Gregory C. Leo、David F. McComsey、Rosemary J. Santulli、Bruce E. Maryanoff

  DOI：10.1021/jo702551t

  日期：2008.3.1

  An improved scale-up synthesis was required for the alpha(V)beta(3)/alpha(V)beta(5) integrin antagonist 1, which had demonstrated oral efficacy in eye disease models of angiogenesis and vascular permeability. A stereodefined, quinoline-substituted, unsaturated ester was conveniently prepared by a Suzuki-Miyaura coupling to facilitate exploration of multiple methods of asymmetric reduction. The catalytic chiral hydrogenation of the corresponding unsaturated acid (Z-5b) with a ruthenium-based metal precursor and the (R)-XylPhanePhos ligand proved particularly efficient and economical. The resulting (3S)-quinoline-containing intermediate was reduced to an equal mixture of tetrahydroquinoline diastereomers. The undesired diastereomer could be recycled to the desired one by an oxidation/reduction protocol. The absolute stereochemistry of 1 was established as 3S,3'S by a combination of X-ray diffraction and chemical means.