Tert-butyl 4-(1-cyano-2-ethoxy-2-oxoethyl)-4-[4-(trifluoromethyl)phenyl]piperidine-1-carboxylate | 878130-29-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: Tert-butyl 4-(1-cyano-2-ethoxy-2-oxoethyl)-4-[4-(trifluoromethyl)phenyl]piperidine-1-carboxylate
• CAS: 878130-29-1
• 化学式: C₂₂H₂₇F₃N₂O₄
• 分子量: 440.463
• InChiKey: XASAPZLFSKUVBH-UHFFFAOYSA-N

物化性质

• 沸点：
  509.9±50.0 °C(Predicted)
• 密度：
  1.214±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  79.6
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Tert-butyl 4-(1-cyano-2-ethoxy-2-oxoethyl)-4-[4-(trifluoromethyl)phenyl]piperidine-1-carboxylate 在 copper(I) oxide 、 水 、 三乙酰氧基硼氢化钠 、 二异丁基氢化铝 、 sodium hydroxide 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 3.5h， 生成
  参考文献：
  名称：

  Novel 4,4-Disubstituted Piperidine-Based C–C Chemokine Receptor-5 Inhibitors with High Potency against Human Immunodeficiency Virus-1 and an Improved human Ether-a-go-go Related Gene (hERG) Profile

  摘要：

  We recently described (J. Med. Chem. 2008, 51, 6538-6546) a novel class of CCR5 antagonists with strong anti-HIV potency. Herein, we detail SAR converting leads 1 and 2 to druglike molecules. The pivotal structural motif enabling this transition was the secondary sulfonamide substituent. Further fine-tuning of the substituent pattern in the sulfonamide paved the way to enhancing potency and bioavailability and minimizing hERG inhibition, resulting in discovery of clinical compound 122 (GSK163929).

  DOI：

  10.1021/jm200279v
• 作为产物：
  描述：

  氰乙酸乙酯 在 copper(l) iodide 、 ammonium acetate 、 溶剂黄146 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 6.0h， 生成 Tert-butyl 4-(1-cyano-2-ethoxy-2-oxoethyl)-4-[4-(trifluoromethyl)phenyl]piperidine-1-carboxylate
  参考文献：
  名称：

  Novel 4,4-Disubstituted Piperidine-Based C–C Chemokine Receptor-5 Inhibitors with High Potency against Human Immunodeficiency Virus-1 and an Improved human Ether-a-go-go Related Gene (hERG) Profile

  摘要：

  We recently described (J. Med. Chem. 2008, 51, 6538-6546) a novel class of CCR5 antagonists with strong anti-HIV potency. Herein, we detail SAR converting leads 1 and 2 to druglike molecules. The pivotal structural motif enabling this transition was the secondary sulfonamide substituent. Further fine-tuning of the substituent pattern in the sulfonamide paved the way to enhancing potency and bioavailability and minimizing hERG inhibition, resulting in discovery of clinical compound 122 (GSK163929).

  DOI：

  10.1021/jm200279v

文献信息

• Synthesis of 4‐Substituted Piperidines via a Mild and Scalable Two‐Step Cu₂O‐Mediated Decarboxylation of Cyanoesters
  作者：Brian A. Chauder、Eric E. Boros、Kien S. Du、Wieslaw M. Kazmierski、Cecilia S. Koble、James B. Thompson、Elie A. Tabet

  DOI：10.1080/00397910500374971

  日期：2006.1

  Abstract A four‐step, high‐yielding, kilogram‐scale protocol to prepare aldehyde 5 is reported. The key reaction is a mild, two‐step Cu2O‐mediated decarboxylation of cyanoester 3 that proceeds in excellent yield. The general applicability of this methodology has also been explored.

  摘要 报道了制备醛 5 的四步、高产、公斤级方案。关键反应是温和的、两步 Cu2O 介导的氰基酯 3 脱羧反应，该反应以优异的产率进行。还探讨了这种方法的普遍适用性。