methyl 2,6-bis(4-chlorophenyl)-1-(4-fluorophenyl)-4-(4-fluorophenylamino)-1,2,5,6-tetrahydropyridine-3-carboxylate

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: methyl 2,6-bis(4-chlorophenyl)-1-(4-fluorophenyl)-4-(4-fluorophenylamino)-1,2,5,6-tetrahydropyridine-3-carboxylate
• 英文别名: ethyl (2S,6R)-2,6-bis(4-chlorophenyl)-4-(4-fluoroanilino)-1-(4-fluorophenyl)-3,6-dihydro-2H-pyridine-5-carboxylate
• 化学式: C₃₂H₂₆Cl₂F₂N₂O₂
• 分子量: 579.473
• InChiKey: VNIABXFLSKCNND-IGYGKHONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.2
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  乙酰乙酸乙酯 、 4-氯苯甲醛 、 4-氟苯胺 在 酒石酸 作用下， 以 甲醇 为溶剂， 反应 7.0h， 以80%的产率得到methyl 2,6-bis(4-chlorophenyl)-1-(4-fluorophenyl)-4-(4-fluorophenylamino)-1,2,5,6-tetrahydropyridine-3-carboxylate
  参考文献：
  名称：

  酒石酸：一锅合成功能化哌啶的天然，绿色高效催化剂

  摘要：

  摘要 酒石酸是一种高效和高效的催化剂，用于在室温下通过甲醇中1,3-二羰基化合物，芳族醛和各种胺的组合一锅合成高取代的哌啶。该方案的优点是收率高，反应时间短，反应条件温和，无需柱色谱法，操作简便，后处理步骤简单，催化剂便宜且可生物降解。 图形概要

  DOI：

  10.1007/s11164-014-1877-1

文献信息

• Bismuth nitrate-catalyzed multicomponent reaction for efficient and one-pot synthesis of densely functionalized piperidine scaffolds at room temperature
  作者：Goutam Brahmachari、Suvankar Das

  DOI：10.1016/j.tetlet.2012.01.042

  日期：2012.3

  diastereoselective multicomponent one-pot synthesis of a series of pharmaceutically interesting functionalized piperidine derivatives has been developed based on a low-cost and environmentally benign Bi(NO3)3·5H2O catalyst via tandem reactions of 1,3-dicarbonyl compounds, aromatic aldehydes, and various amines in ethanol at room temperature. High atom-economy, good yields, eco-friendliness, and mild reaction conditions

  基于低成本和环境友好的Bi（NO 3）3 ·5H 2 O催化剂，通过串联反应进行了简单，直接和高效的非对映选择性多组分一锅合成一系列可药用的功能化哌啶衍生物。室温下在乙醇中的1,3-二羰基化合物，芳族醛和各种胺。高原子经济性，良好的产率，生态友好性和温和的反应条件是该方案的一些重要特征。
• Y(NO₃)₃·4H₂O-assisted Three-component Synthesis of Polysubstituted Tetrahydropyridines
  作者：Mir Rasul Mousavi、Jasem Aboonajmi、Malek Taher Maghsoodlou、Nourallah Hazeri

  DOI：10.3184/174751914x13890195583234

  日期：2014.2

  A mild and efficient method for the synthesis of polysubstituted tetrahydropyridines has been developed which involves a three-component reaction of an arylamine (2 equiv.), an araldehyde (2 equiv.) and ethyl (or methyl) acetoacetate (1 equiv.) in MeCN under ambient conditions, in the presence of yttrium nitrate, Y(NO₃)₃·4H₂O. This appears to be the first time yttrium nitrate has been used as a catalyst for this type of synthesis of tetrahydropyridines.

  在硝酸钇（Y(NO3)3-4H2O）存在的条件下，在 MeCN 中进行芳胺（2 等份）、芳醛（2 等份）和乙酰乙酸乙酯（或乙酰乙酸甲酯）（1 等份）的三组分反应。这似乎是首次使用硝酸钇作为催化剂合成四氢吡啶类化合物。
• B(C6F5)3 as versatile catalyst: an efficient and mild protocol for the one-pot synthesis of functionalized piperidines and 2-substituted benzimidazole derivatives
  作者：Santosh Kumar Prajapti、Atulya Nagarsenkar、Sravanthi Devi Guggilapu、Bathini Nagendra Babu

  DOI：10.1016/j.tetlet.2015.10.074

  日期：2015.12

  An efficient, mild and environmentally benign protocol has been developed for the diastereoselective one-pot synthesis of functionalized piperidines via tandem reactions of aromatic aldehydes, amines and acetoacetic esters in the presence of a catalytic amount of tris(pentafluorophenyl)borane. Furthermore, B(C6F5)3 was successfully used to catalyze the synthesis of benzimidazole and its derivatives

  在催化量的三（五氟苯基）硼烷的存在下，通过芳族醛，胺和乙酰乙酸酯的串联反应，已经开发了一种高效，温和且对环境有益的方案，用于非对映选择性一锅合成官能化哌啶。此外，B（C 6 F 5）3已成功用于催化苯并咪唑及其衍生物从各种醛和邻苯二胺的合成。另外，本方案的适用性扩展到苯并恶唑和苯并噻唑的合成。
• In vitro evaluation and in silico screening of synthetic acetylcholinesterase inhibitors bearing functionalized piperidine pharmacophores
  作者：Goutam Brahmachari、CheeYan Choo、Pravin Ambure、Kunal Roy

  DOI：10.1016/j.bmc.2015.06.005

  日期：2015.8

  A series of densely functionalized piperidine (FP) scaffolds was synthesized following a diastereoselective one-pot multicomponent protocol under eco-friendly conditions. The FPs were evaluated in vitro for their acetylcholinesterase (AChE) inhibitory activity, and in silico studies for all the target compounds were carried out using pharmacophore mapping, molecular docking and quantitative structure-activity relationship (QSAR) analysis in order to understand the structural features required for interaction with the AChE enzyme and the key active site residues involved in the intermolecular interactions. Halogenation, nitration or 3,4-methylenedixoxy-substitution at the phenyl ring attached to the 2- and 6-positions of 1,2,5,6-tetrahydropyridine nucleus in compounds 14-17, 19, 20, 24 and 26 greatly enhanced the AChE inhibitory activity. The docking analysis demonstrated that the inhibitors are well-fitted in the active sites. The in silico studies enlighten the future course of studies in modifying the scaffolds for better therapeutic efficacy against the deadly Alzheimer's disease. (C) 2015 Elsevier Ltd. All rights reserved.