(-)-(S)-camphanic acid amide of (2S,3'R)-4-piperidin-4-yl-3-(1',2',3',4'-tetrahydroquinolin-3'-yl)butyric acid methyl ester | 1014680-00-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (-)-(S)-camphanic acid amide of (2S,3'R)-4-piperidin-4-yl-3-(1',2',3',4'-tetrahydroquinolin-3'-yl)butyric acid methyl ester
• 英文别名: 4-[1-(4,7,7,-trimethyl-3-oxo-2-oxa-bicyclo[2.2.1]heptane-1-carbonyl)-piperidin-4-yl]-3-[1-(4,7,7-trimethyl-3-oxo-2-oxa-bicyclo[2.2.1]heptane-1-carbonyl)-1,2,3,4-tetrahydro-quinolin-3-yl]-butyric acid methyl ester；methyl (3S)-3-[(3R)-1-[(1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbonyl]-3,4-dihydro-2H-quinolin-3-yl]-4-[1-[(1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbonyl]piperidin-4-yl]butanoate
• CAS: 1014680-00-2
• 化学式: C₃₉H₅₂N₂O₈
• 分子量: 676.85
• InChiKey: HLJZYOBUPHPYTP-QUTRRMAKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  49
• 可旋转键数：
  8
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  120
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-哌啶-4-基-3-(1,2,3,4-四氢喹啉-3-基)-丁酸甲酯 、 (1S)-(-)-莰烷酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以68%的产率得到(-)-(S)-camphanic acid amide of (2S,3'R)-4-piperidin-4-yl-3-(1',2',3',4'-tetrahydroquinolin-3'-yl)butyric acid methyl 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

文献信息

• 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.