(R)-4-(3-methoxy-carbonyl-2-quinolin-3-yl-propyl)piperidine-1-carboxylic acid tert-butyl ester | 1149753-96-7

• 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
• 英文名称: (R)-4-(3-methoxy-carbonyl-2-quinolin-3-yl-propyl)piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 4-[(2R)-4-methoxy-4-oxo-2-quinolin-3-ylbutyl]piperidine-1-carboxylate
• CAS: 1149753-96-7
• 化学式: C₂₄H₃₂N₂O₄
• 分子量: 412.529
• InChiKey: XDGLIEJJVPSXHD-LJQANCHMSA-N

物化性质

• 沸点：
  532.6±25.0 °C(predicted)
• 密度：
  1.133±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  68.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-(3-methoxycarbonyl-2-quinolin-3-ylallyl)piperidine-1-carboxylic acid tert-butyl ester 在 (R)-N-diphenylphosphino-N-[(R)-1-phenylethyl]-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethylamine 、 chlorobis(ethylene)rhodium(I) dimer 氢气 作用下， 以 1,2-二氯乙烷 为溶剂， 20.0~50.0 ℃ 、2.58 MPa 条件下， 反应 18.0h， 以90%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

• 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.
• Synthesis of an αvβ3 integrin antagonist intermediate via asymmetric hydrogenation of an α,β-unsaturated ester with BoPhoz-iridium and BoPhoz-rhodium catalysts
  作者：Antonio Zanotti-Gerosa、William A. Kinney、Gabriela A. Grasa、Jonathan Medlock、Andreas Seger、Shyamali Ghosh、Christopher A. Teleha、Bruce E. Maryanoff

  DOI：10.1016/j.tetasy.2008.03.031

  日期：2008.5

  The enantioselective synthesis of an alpha(v)beta(3) integrin antagonist intermediate was approached via asymmetric hydrogenation of a beta,beta-disubstituted-alpha,beta-unsaturated ester. As a result of the rapid parallel screening of a selection of ligands and catalysts, we found that neutral Me-BoPhoz-rhodium and iridium catalysts effect the required transformation with a high enantioselectivity. Both the activity and selectivity of the catalysts were strongly dependent on the choice of solvent and counter-ion. The addition of iodine modified the iridium catalyst such that the reduction of the 3-substituted quinoline ring took place. (C) 2008 Elsevier Ltd. All rights reserved.
• 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。