ethyl 2,6-bis(4-chlorophenyl)-1-(4-fluorophenyl)-4-((4-fluorophenyl)amino)-1,2,5,6-tetrahydropyridine-3-carboxylate | 1413946-27-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: ethyl 2,6-bis(4-chlorophenyl)-1-(4-fluorophenyl)-4-((4-fluorophenyl)amino)-1,2,5,6-tetrahydropyridine-3-carboxylate
• 英文别名: ethyl 2,6-bis(4-chlorophenyl)-4-(4-fluoroanilino)-1-(4-fluorophenyl)-3,6-dihydro-2H-pyridine-5-carboxylate
• CAS: 1413946-27-6
• 化学式: C₃₂H₂₆Cl₂F₂N₂O₂
• 分子量: 579.473
• InChiKey: VNIABXFLSKCNND-UHFFFAOYSA-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 Iron(III) nitrate nonahydrate 作用下， 以 乙醇 为溶剂， 反应 8.5h， 以83%的产率得到ethyl 2,6-bis(4-chlorophenyl)-1-(4-fluorophenyl)-4-((4-fluorophenyl)amino)-1,2,5,6-tetrahydropyridine-3-carboxylate
  参考文献：
  名称：

  Fe（NO3）3·9H2O单锅合成高官能化哌啶的高效催化剂

  摘要：

  Fe（NO 3）3 ·9H 2 O可作为一种有效的催化剂，用于在环境温度下由芳族醛，苯胺和b-酮酸酯在乙醇中一锅三组分合成高度官能化的哌啶。该程序包括一些重要方面，例如易于处理，无需柱色谱，简单易用的前体以及良好到高收率。

  DOI：

  10.1002/jccs.201200421

文献信息

• TiCl₂·2H₂O catalyzed one-pot synthesis of highly functionalized tetrahydropiperidines and evaluation of their antimicrobial activities
  作者：Mohsen Abbasi、Seyed Mohammad Seyedi、Hamid Sadeghian、Maryam Akhbari、Mohammadreza Enayaty、Ali Shiri

  DOI：10.1515/hc-2015-0081

  日期：2016.6.1

  One-pot condensation reaction of ethyl acetoacetate, various substituted benzaldehydes and anilines in the presence of TiCl₂·2H₂O yields highly functionalized tetrahydropiperidines. Atom economy, efficiency, and short reaction times are the advantages of the method, which is carried out under mild conditions using easily accessible and inexpensive chemicals. The antimicrobial activity of the synthesized products was evaluated against three Gram-positive and three Gram-negative bacteria, a yeast and a fungus strain using disc diffusion and minimum inhibitory concentration methods.

  一锅法合成反应中，乙酰乙酸乙酯、各种取代苯甲醛和苯胺在TiCl2·2H2O存在下反应，生成高度官能化的四氢哌啶。该方法具有原子经济性、效率高和反应时间短的优点，采用易得且廉价的化学品在温和条件下进行。合成产物的抗菌活性通过盘扩散和最小抑制浓度方法评估，对三种革兰氏阳性细菌、三种革兰氏阴性细菌、一种酵母和一种真菌菌株进行了测试。
• Cyanuric chloride catalyzed metal-free mild protocol for the synthesis of highly functionalized tetrahydropyridines
  作者：Rathinam Ramesh、Subramani Maheswari、Mani Arivazhagan、Jan Grzegorz Malecki、Appaswami Lalitha

  DOI：10.1016/j.tetlet.2017.08.074

  日期：2017.10

  condensation of ethyl acetoacetate, anilines and aromatic aldehydes under mild reaction conditions has been described. This domino strategy allows rapid cyclization in the presence of 10 mol% of cyanuric chloride as a source of hydrochloric acid to afford the desired target skeletons in excellent yields. The present protocol offers prominent advantages of simple operational procedure, metal-free organocatalyst

  环境友好，容易和优雅的合成方法进行了一系列不同的2,6-二芳基四氢吡啶-3-羧酸盐的方便访问经由一釜，乙酰乙酸乙酯，苯胺和在温和的芳香醛的伪五组分缩合已经描述了反应条件。这种多米诺骨牌策略允许在10摩尔％的氰尿酰氯作为盐酸源的情况下快速环化，从而以优异的收率提供所需的目标骨架。本协议提供了以下优点：操作步骤简单，无金属的有机催化剂，实用且坚固的基材范围。
• Silica Sulfuric Acid-Catalyzed Five-component Efficient Synthesis of Five-Substituted Tetrahydropyridines
  作者：Xiao-xiao Zhang、Yu Wan、Li-ling Pang、Hai-ying Wang、Ling-ling Zhao、Chao Wang、Shu Ying Hang、Gui Xiang Liu、Liang-Feng Chen、Hui Wu

  DOI：10.1002/jhet.1744

  日期：2014.3

  A highly atom‐economic one‐pot synthesis of five‐substituted tetrahydropyridines via a five‐component condensation of two equivalents of aromatic aldehyde, two equivalents of aromatic aniline, and one equivalent of β‐keto ester catalyzed by silica sulfuric acid is reported. In this reaction, up to five new bonds and one new ring were formed in one pot with water as the only one by‐product.

  据报道，一种高原子经济的一锅法合成方法是通过二当量的芳族醛，两当量的芳族苯胺和一当量的二氧化硅硫酸催化的五组分缩合反应来合成五取代的四氢吡啶。在该反应中，在一个锅中最多只有五个副产物形成了五个新的键和一个新的环。
• Mohammadi, Seddigheh; Ghazanfari, Dadkhoda; Karimi-Jaberi, Zahed, Revue Roumaine de Chimie, 2017, vol. 62, # 11, p. 825 - 829
  作者：Mohammadi, Seddigheh、Ghazanfari, Dadkhoda、Karimi-Jaberi, Zahed

  DOI：——

  日期：——
• Highly functionalized tetrahydropyridines are cytotoxic and selective inhibitors of human puromycin sensitive aminopeptidase
  作者：Raghunath Aeluri、Roopa Jones Ganji、Anil Kumar Marapaka、Vijaykumar Pillalamarri、Manjula Alla、Anthony Addlagatta

  DOI：10.1016/j.ejmech.2015.10.026

  日期：2015.12

  Efficient one-pot five-component synthetic protocols for highly functionalized tetrahydropyridines (THPs) and their biological evaluation have been illustrated. Synthesis of novel functionalized tetrahydropyridines containing differential substitutions at 2,6-positions has been achieved via a modified MCR. Cytotoxic studies of 23 synthesized compounds have been carried out against three different cell lines, namely A-549, HeLa and HepG2, wherein some compounds have displayed appreciable cytotoxicity. Further, investigation of enzyme inhibition by the synthesized THPs has been carried out against four members of M1 family aminopeptidases. Several compounds have selectively inhibited only one member of this enzyme family i.e., human puromycin sensitive aminopeptidase (hPSA). Among the compounds; 4h, 9b, 9e and 10a demonstrated best inhibition against hPSA. (C) 2015 Elsevier Masson SAS. All rights reserved.