(R)-4-(3-羧基-2-喹啉-3-基丙基)哌啶-1-羧酸叔丁酯 | 1062157-59-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: (R)-4-(3-羧基-2-喹啉-3-基丙基)哌啶-1-羧酸叔丁酯
• 英文名称: (R)-4-(3-carboxy-2-quinolin-3-ylpropyl)piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: 4-(3-carboxy-2-quinolin-3-yl-propyl)piperidine-1-carboxylic acid tert-butyl ester
• CAS: 1062157-59-8
• 化学式: C₂₃H₃₀N₂O₄
• 分子量: 398.502
• InChiKey: ZUOHZQHZAIIHMK-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.83
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  79.73
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (R)-4-(3-羧基-2-喹啉-3-基丙基)哌啶-1-羧酸叔丁酯 、 三甲基硅烷化重氮甲烷 以 甲醇 、 乙醚 为溶剂， 生成 (R)-4-(3-methoxy-carbonyl-2-quinolin-3-yl-propyl)piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Enantioselective process for preparing a substituted alkanoic acid

  摘要：

  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。

  公开号：

  US20090124804A1
• 作为产物：
  描述：

  4-[1-[(2-Methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]-3-quinolin-3-ylbut-2-enoic acid 在 (S)-Xyl-PhanePhos/[RuCl₂(DMF)2] 氢气 、 三乙胺 作用下， 以 甲醇 为溶剂， 60.0 ℃ 、3.07 MPa 条件下， 反应 20.0h， 以82%的产率得到
  参考文献：
  名称：

  Enantioselective process for preparing a substituted alkanoic acid

  摘要：

  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。

  公开号：

  US20090124804A1

文献信息

• Efficient, enantioselective synthesis of a β,β-disubstituted carboxylic acid by Ru-XylPhanePhos-catalyzed asymmetric hydrogenation
  作者：Gabriela A. Grasa、Antonio Zanotti-Gerosa、Shyamali Ghosh、Christopher A. Teleha、William A. Kinney、Bruce E. Maryanoff

  DOI：10.1016/j.tetlet.2008.06.068

  日期：2008.9

  integrin antagonist intermediate was accomplished via catalytic asymmetric hydrogenation of the corresponding β,β-disubstituted α,β-unsaturated carboxylic acid bearing a 3-quinolinyl moiety. The successful application of a Ru-(R)-XylPhanePhos catalyst to this type of substrate is unprecedented. In situ NMR experiments of pre-catalyst formation/activation by CH3CO2H, and reaction parameter modification,

  一个关键的α对映选择性制备v β 3整联蛋白拮抗剂的中间体通过相应的β的催化不对称氢化，β二取代的α，β不饱和羧酸轴承3-喹啉基部分来实现。Ru- （R）-XylPhanePhos催化剂在此类基材上的成功应用是前所未有的。CH 3 CO 2 H催化前催化剂形成/活化及反应参数修饰的原位NMR实验表明，[Ru（COD）（CF 3 CO 2）2 ] 2 /（R）-XylPhanePhos具有很高的活性，且高效的催化系统。
• 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.