phenyl(4-(pyridin-2-yl)piperazin-1-yl)methanone | 166438-06-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: phenyl(4-(pyridin-2-yl)piperazin-1-yl)methanone
• 英文别名: 1-(benzoyl)-4-(pyridin-2-yl)piperazine；Phenyl 4-(2-pyridyl)piperazinyl ketone；phenyl-(4-pyridin-2-ylpiperazin-1-yl)methanone
• CAS: 166438-06-8
• 化学式: C₁₆H₁₇N₃O
• 分子量: 267.33
• InChiKey: DODMPXGYBRIUJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  36.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  五氟苯 、 phenyl(4-(pyridin-2-yl)piperazin-1-yl)methanone 在 2,2'-硫代二丙烷 、 palladium diacetate 、 silver carbonate 作用下， 以 1,4-二氧六环 为溶剂， 以62 %的产率得到(4-(5-(perfluorophenyl)pyridin-2-yl)piperazin-1-yl)(phenyl)methanone
  参考文献：
  名称：

  Direct C(3)5−H Polyfluoroarylation of 2‐Amino/alkoxy Pyridines Enabled by a Transient and Electron‐deficient Palladium Intermediate

  摘要：

  摘要在本文中，我们介绍了一种前所未有的偶氮限制的 2- 氨基吡啶的 C5-H 多氟芳基化反应，该反应通过 C-H/C-H 偶联由瞬时缺电子的全氟化芳基钯物种实现。该方案还首次实现了立体学和电子学指导下的 2-烷氧基吡啶的 C3(5)-H 多氟芳基化。药物、药物衍生物和天然产物衍生物的后期 C-H 功能化以及 C5 芳基药物衍生物的合成进一步证明了该方法的实用性。初步机理研究表明，笨重但亲电的全氟芳基钯物种与 2-氨基/烷氧基吡啶的 C5 位部分亲核性的协同组合是反应性和选择性的源泉。重要的是，实验首次证明了二异丙基硫醚的作用。

  DOI：

  10.1002/chem.202301436
• 作为产物：
  描述：

  苯甲酸甲酯 、 1-(2-吡啶基)哌嗪 在 bis(1,5-cyclooctadiene)nickel (0) 、 1,3-bis(2,6-diisopropylphenyl)imidazolium 作用下， 以 甲苯 为溶剂， 反应 16.0h， 以91%的产率得到phenyl(4-(pyridin-2-yl)piperazin-1-yl)methanone
  参考文献：
  名称：

  由甲基酯形成镍催化的酰胺键

  摘要：

  尽管是最重要且经常进行的化学反应之一，酰胺键的合成主要通过浪费的方法完成，该浪费的方法是通过化学计量活化一种原料而进行的。我们报道了一种镍催化的方法，该方法可以使从丰富的甲酯原料中合成出各种酰胺，仅产生化学计量废品的挥发性醇。与酸和碱介导的酰胺化反应相反，该反应被认为是通过中性的交叉偶联型机理进行的，从而为直接，有效，化学选择性的合成开辟了新的机会。

  DOI：

  10.1002/anie.201808560

文献信息

• Catalytic N‐Acylation of Cyclic Amines by Arylglyoxylic Acids via Radical‐Radical Cross‐Coupling
  作者：Ajijur Rahaman、Anupam Kumar Singh、Aniket Gupta、Sukalyan Bhadra

  DOI：10.1002/ejoc.202100381

  日期：2021.4.22

  A unique copper‐based catalyst system allows for the N‐acylation of cyclic amines by arylglyoxylic acids via radical‐radical cross‐coupling strategy. As evidenced by EPR, UV‐Vis, and mass spectrometric analysis, the amide linkage formation proceeds through a Cu(I)/Cu(II) catalytic cycle involving a twofold SET process.

  独特的铜基催化剂体系可通过自由基-自由基交叉偶联策略使芳基乙醛酸对环胺进行N酰化。正如EPR，UV-Vis和质谱分析所证明的那样，酰胺键的形成过程通过涉及双重SET过程的Cu（I）/ Cu（II）催化循环进行。
• Arylpiperazines for Management of Benign Prostatic Hyperplasia: Design, Synthesis, Quantitative Structure−Activity Relationships, and Pharmacokinetic Studies
  作者：Amit Sarswat、Rajeev Kumar、Lalit Kumar、Nand Lal、Smriti Sharma、Yenamandra S. Prabhakar、Shailendra K. Pandey、Jawahar Lal、Vikas Verma、Ashish Jain、Jagdamba P. Maikhuri、Diwakar Dalela、Kirti、Gopal Gupta、Vishnu L. Sharma

  DOI：10.1021/jm101163m

  日期：2011.1.13

  A series of 27 aryl/heteroaryl/aralkyl/aroyl piperazines were synthesized, and most of these compounds reduced prostate weight of mature rats by 15-47% Three compounds, 10, 12, and 18, had better activity profile (reduced prostate weight by 47%, 43%, and 39%, respectively) than the standard drug flutamide (24% reduction) QSAR suggested structures with more cyclic and branched moieties, increased topological separation of 0 and N therein, and reduced solvation connectivity index for better activity Pharmacokinetic study with compound 10 at an oral dose of 10 0 mg/kg indicated good absorption, negligible extrahepatic elimination, and rapid distribution to the target organ (prostate) but restricted entry through the blood brain barrier A 10-fold decrease in PSA and 15-fold increase in ER-beta gene expressions of human prostate cancer cells (LNCaP) by compound 10 in vitro indicated AR and ER-beta mediated actions The findings may stimulate further explorations of identified lead for the management of benign prostatic hyperplasia
• Synthesis and solid state study of pyridine- and pyrimidine-based fragment libraries
  作者：John Spencer、Hiren Patel、Samantha K. Callear、Simon J. Coles、John J. Deadman

  DOI：10.1016/j.tetlet.2011.07.147

  日期：2011.11

  A library of pyridines and pyrimidines has been synthesised in excellent yields employing microwave and flow chemistry methodologies. Work-up bottlenecks have been facilitated substantially by the use of supported reagents and many of the final compounds have been studied in the solid state by single crystal X-ray diffraction. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.
• Nickel-Catalyzed Amide Bond Formation from Methyl Esters
  作者：Taoufik Ben Halima、Jeanne Masson-Makdissi、Stephen G. Newman

  DOI：10.1002/anie.201808560

  日期：2018.9.24

  reactions, the synthesis of amide bonds is accomplished primarily by wasteful methods that proceed by stoichiometric activation of one of the starting materials. We report a nickel‐catalyzed procedure that can enable diverse amides to be synthesized from abundant methyl ester starting materials, producing only volatile alcohol as a stoichiometric waste product. In contrast to acid‐ and base‐mediated amidations

  尽管是最重要且经常进行的化学反应之一，酰胺键的合成主要通过浪费的方法完成，该浪费的方法是通过化学计量活化一种原料而进行的。我们报道了一种镍催化的方法，该方法可以使从丰富的甲酯原料中合成出各种酰胺，仅产生化学计量废品的挥发性醇。与酸和碱介导的酰胺化反应相反，该反应被认为是通过中性的交叉偶联型机理进行的，从而为直接，有效，化学选择性的合成开辟了新的机会。
• Direct C(3)5−H Polyfluoroarylation of 2‐Amino/alkoxy Pyridines Enabled by a Transient and Electron‐deficient Palladium Intermediate
  作者：Animesh Das、Biplab Maji

  DOI：10.1002/chem.202301436

  日期：2023.7.20

  Herein, we present an unprecedented azine‐limited C5−H polyfluoroarylation of 2‐aminopyridines enabled by a transient and electron‐deficient perfluoroaryl‐Pd species via C−H/C−H coupling. The protocol further allows C3(5)−H polyfluoroarylation of 2‐alkoxypyridines guided by sterics and electronics for the first time. The late‐stage C−H functionalization of drugs, drug derivatives, and natural product derivatives and synthesis of C5‐aryl drug derivatives further demonstrated the method's utility. The preliminary mechanistic studies reveal that the synergistic combination of the bulky yet electrophilic perfluoroaryl‐Pd species and the partial nucleophilicity of the C5‐position of 2‐amino/alkoxy‐pyridines is the origin of reactivity and selectivity. Importantly, the first experimental evidence for the role of diisopropyl sulfide is provided.

  摘要在本文中，我们介绍了一种前所未有的偶氮限制的 2- 氨基吡啶的 C5-H 多氟芳基化反应，该反应通过 C-H/C-H 偶联由瞬时缺电子的全氟化芳基钯物种实现。该方案还首次实现了立体学和电子学指导下的 2-烷氧基吡啶的 C3(5)-H 多氟芳基化。药物、药物衍生物和天然产物衍生物的后期 C-H 功能化以及 C5 芳基药物衍生物的合成进一步证明了该方法的实用性。初步机理研究表明，笨重但亲电的全氟芳基钯物种与 2-氨基/烷氧基吡啶的 C5 位部分亲核性的协同组合是反应性和选择性的源泉。重要的是，实验首次证明了二异丙基硫醚的作用。