1-(4-methylpiperazin-1-yl)-3-phenylisoquinoline

• 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: 1-(4-methylpiperazin-1-yl)-3-phenylisoquinoline
• 化学式: C₂₀H₂₁N₃
• 分子量: 303.407
• InChiKey: IWNXRLLJQNKLRQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  19.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N,N,2-三甲基-苯甲酰胺 在 potassium carbonate 、 lithium diisopropyl amide 、 三氯氧磷 作用下， 生成 1-(4-methylpiperazin-1-yl)-3-phenylisoquinoline
  参考文献：
  名称：

  Synthesis and biological evaluation of 3-arylisoquinolines as antitumor agents

  摘要：

  To investigate the structure-activity relationship of 7,8-dimethoxy-2-methyl-3-(4,5-methylenedioxy-2-vinylphenyl)isoquinolin-1(2H)-one 2, diverse substituted 3-arylisoquinolines were synthesized and tested in vitro antitumor activity against five human tumor cell lines. The results showed a broad antitumor spectrum for a series of 3-arylisoquinolines. (C) 1997 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(97)10190-1

文献信息

• Selective Phosphoranation of Unactivated Alkynes with Phosphonium Cation To Achieve Isoquinoline Synthesis
  作者：Hong Cui、Jinku Bai、Tianyu Ai、Ye Zhan、Guanzhong Li、Honghua Rao

  DOI：10.1021/acs.orglett.1c01237

  日期：2021.5.21

  a selective phosphoranation of alkynes with phosphonium cation, which directs a concise approach to isoquinolines from unactivated alkyne and nitrile feedstocks in a single step. Mechanistic studies suggest that the annulation reaction is initiated by the unprecedented phosphoranation of alkynes, thus representing a unique reaction pattern of phosphonium salts and distinguishing it from existing protocols

  我们在本文中开发了用phospho阳离子对炔烃进行选择性磷酸化的方法，该方法可在一个步骤中从未活化的炔烃和腈类原料中直接引入异喹啉的简便方法。机理研究表明，环化反应是由炔烃的空前磷酸化作用引发的，因此代表了salts盐的独特反应模式，并将其与主要依赖于利用高度官能化的亚胺/肟和/或高度极化的炔烃的现有方案相区别。
• Highly Regioselective Isoquinoline Synthesis via Nickel-Catalyzed Iminoannulation of Alkynes at Room Temperature
  作者：Jian-Guo Sun、Xiao-Yu Zhang、Hua Yang、Ping Li、Bo Zhang

  DOI：10.1002/ejoc.201800341

  日期：2018.9.23

  The air‐stable and inexpensive Ni(dppe)Cl2 along with Et3N efficiently catalyzes the iminoannulation of alkynes at room temperature, allowing for the preparation of important 3,4‐disubstituted and 3‐substituted isoquinolines in high yields with complete regioselectivity. These annulation reactions feature a broad substrate scope, easy scalability, operational simplicity, and excellent practicality

  空气稳定且价格便宜的Ni（dppe）Cl 2以及Et 3 N在室温下可有效催化炔烃的亚氨基环化反应，从而可以高收率和完全的区域选择性制备重要的3,4-二取代和3-取代的异喹啉。这些成环反应的特点是基材范围广，可扩展性强，操作简便且实用性强。
• Me₃Al-mediated domino nucleophilic addition/intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines; a convenient approach for the synthesis of substituted 1-aminoisoquinolines
  作者：Krishna M S Adusumalli、Lakshmi N S Konidena、Hima B Gandham、Krishnaiah Kumari、Krishna R Valluru、Satya K R Nidasanametla、Venkateswara R Battula、Hari K Namballa

  DOI：10.3762/bjoc.17.186

  日期：——

  amines in the presence of Me3Al. The reaction proceeds via a domino nucleophilic addition with subsequent intramolecular cyclisation. This method provides a wide variety of substituted 1-aminoisoquinolines with good functional group tolerance. Furthermore, the synthetic utility of this protocol was demonstrated in the successful synthesis of the antitumor agent CWJ-a-5 in gram scale.

  通过在 Me 3 Al存在下用胺处理 2-(2-oxo-2-苯乙基) 苄腈，实现了一种用于构建 1-氨基异喹啉的简单有效的方案。该反应通过多米诺亲核加成和随后的分子内环化进行。该方法提供了多种具有良好官能团耐受性的取代 1-氨基异喹啉。此外，该协议的合成效用在克级抗肿瘤剂 CWJ-a-5 的成功合成中得到了证明。
• Catalyst-Controlled Regioselective Approach to 1-Aminoisoquinolines and/or 1-Aminoisoindolines through Aminative Domino Cycliza­tion of 2-Alkynylbenzonitriles
  作者：Virsinha Reddy、Abhijeet S. Jadhav、Ramasamy Vijaya Anand

  DOI：10.1002/ejoc.201501390

  日期：2016.1

  A metal-catalyzed regioselective approach towards the synthesis of 1-aminoisoquinolines and/or 1-aminoisindolines through aminative domino cyclization of 2-alkynylbenzonitriles with secondary amines has been developed under solvent-free conditions. It was found that the regioselectivity of the reaction was greatly influenced by the choice of the metal catalyst. Copper-based catalysts favored 6-endo-dig

  已经在无溶剂条件下开发了一种金属催化的区域选择性方法，用于通过 2-炔基苄腈与仲胺的氨基化多米诺环化来合成 1-氨基异喹啉和/或 1-氨基异吲哚啉。发现反应的区域选择性受金属催化剂的选择影响很大。铜基催化剂有利于 6-endo-dig 环化产生 1-氨基异喹啉，而其他催化剂如 Zn、Ag、Bi、Sc 和 Yb 的三氟甲磺酸盐有利于通过 5-exo-dig 环化形成 1-氨基异二氢吲哚。
• Tandem Addition/Cyclization for Access to Isoquinolines and Isoquinolones via Catalytic Carbopalladation of Nitriles
  作者：Linjun Qi、Kun Hu、Shuling Yu、Jianghe Zhu、Tianxing Cheng、Xiaodong Wang、Jiuxi Chen、Huayue Wu

  DOI：10.1021/acs.orglett.6b03499

  日期：2017.1.6

  sequential nucleophilic addition followed by an intramolecular cyclization of functionalized nitriles with arylboronic acids has been achieved, providing an efficient synthetic pathway to access structurally diverse isoquinolines and isoquinolones. This methodology has also been successfully applied to the total synthesis of the topoisomerase I inhibitor CWJ-a-5 (free base).

  已经实现了钯催化的连续亲核加成，然后用芳基硼酸进行分子内官能化腈分子内环化的第一个例子，从而提供了一种有效的合成途径，以获取结构多样的异喹啉和异喹啉酮。该方法也已成功应用于拓扑异构酶I抑制剂CWJ-a-5（游离碱）的全合成。