Tert-butyl 4-(3-fluorophenyl)-4-(2-oxoethyl)piperidine-1-carboxylate | 878130-44-0

• 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-(3-fluorophenyl)-4-(2-oxoethyl)piperidine-1-carboxylate
• CAS: 878130-44-0
• 化学式: C₁₈H₂₄FNO₃
• 分子量: 321.392
• InChiKey: KPTXCEIIEPRIQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Tert-butyl 4-(3-fluorophenyl)-4-(2-oxoethyl)piperidine-1-carboxylate 在 2,2,6,6-四甲基哌啶氧化物 titanium(IV) isopropylate 、 sodium hypochlorite 、 sodium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 6.34h， 生成 (4,6-dimethyl-pyrimidin-5-yl)-(5-{2-[4-(3-fluoro-phenyl)-1-methanesulfonyl-piperidin-4-yl]-1-methyl-ethyl}-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-methanone
  参考文献：
  名称：

  WO2008/34731

  摘要：

  公开号：
• 作为产物：
  描述：

  间溴氟苯 在 copper(I) oxide 、 sodium hydroxide 、 二异丁基氢化铝 、 magnesium 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 8.0h， 生成 Tert-butyl 4-(3-fluorophenyl)-4-(2-oxoethyl)piperidine-1-carboxylate
  参考文献：
  名称：

  通过温和且可扩展的两步 Cu2O 介导的氰酯脱羧合成 4-取代哌啶

  摘要：

  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。

  DOI：

  10.1080/00397910500374971

文献信息

• Discovery of N-benzyl-N′-(4-pipyridinyl)urea CCR5 antagonists as anti-HIV-1 agents (I): Optimization of the amine portion
  作者：Maosheng Duan、Jennifer Peckham、Mark Edelstein、Robert Ferris、Wieslaw M. Kazmierski、Andrew Spaltenstein、Pat Wheelan、Zhiping Xiong

  DOI：10.1016/j.bmcl.2010.10.033

  日期：2010.12

  Several series of carbamate, urea and carboxamide-based CCR5 antagonists have been discovered via optimizations at the amine portion of lead compound 2. All compounds were evaluated for their antiviral activities. Lead urea 29 showed good pharmacokinetic properties, justifying further development of this series. (C) 2010 Elsevier Ltd. All rights reserved.
• 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
  作者：Wieslaw M. Kazmierski、Don L. Anderson、Christopher Aquino、Brian A. Chauder、Maosheng Duan、Robert Ferris、Terrence Kenakin、Cecilia S. Koble、Dan G. Lang、Maggie S Mcintyre、Jennifer Peckham、Christian Watson、Pat Wheelan、Andrew Spaltenstein、Mary B. Wire、Angilique Svolto、Michael Youngman

  DOI：10.1021/jm200279v

  日期：2011.6.9

  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).
• Discovery of N-benzyl-N′-(4-pipyridinyl)urea CCR5 antagonists as anti-HIV-1 agents (II): Modification of the acyl portion
  作者：Maosheng Duan、Jennifer Peckham、Mark Edelstein、Robert Ferris、Wieslaw M. Kazmierski、Andrew Spaltenstein、Pat Wheelan、Zhiping Xiong

  DOI：10.1016/j.bmcl.2010.10.042

  日期：2010.12

  Modification of the acyl moiety in the CCR5 lead molecule 2 led to identification of several new classes of CCR5 antagonists. Antiviral activity and pharmacokinetic properties of the synthesized compounds were evaluated. Structure-activity relationship (SAR) derived from these studies further guided the optimization efforts, ultimately leading to the discovery of 36 with an acceptable drug-like profile. (C) 2010 Elsevier Ltd. All rights reserved.
• WO2008/34731
  申请人：——

  公开号：——

  公开（公告）日：——
• 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。