4-(4-methylquinolin-2-yl)morpholine | 79140-31-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-(4-methylquinolin-2-yl)morpholine
• 英文别名: 4-methyl-2-(4-morpholinyl)quinoline；4-methyl-2-morpholin-4-yl-quinoline；4-Methyl-2-morpholino-chinolin；2-Morpholino-lepidin；4-Methyl-2-morpholinoquinoline
• CAS: 79140-31-1
• 化学式: C₁₄H₁₆N₂O
• mdl: MFCD00817927
• 分子量: 228.294
• InChiKey: WCPAHVWKDJNTDJ-UHFFFAOYSA-N

物化性质

• 沸点：
  181-182.5 °C(Press: 3.5 Torr)
• 密度：
  1.162±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.357
• 拓扑面积：
  25.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-methylquinolin-2-yl)morpholine 在 palladium on activated charcoal 氢气 、 硝酸 作用下， 以 四氢呋喃 为溶剂， 反应 13.0h， 生成 6-amino-4-methyl-2-(4-morpholinyl)quinoline
  参考文献：
  名称：

  6-Acylamino-2-aminoquinolines as Potent Melanin-Concentrating Hormone 1 Receptor Antagonists. Identification, Structure−Activity Relationship, and Investigation of Binding Mode

  摘要：

  Novel 6-acylamino-2-aminoquinoline melanin-concentrating hormone 1 receptor (MCHIR) antagonists were identified by sequential in silico screening with 3D pharmacophore models derived from a series of benzamide antagonists. The structure- activity relationship exploration by synthesis of analogues found structural demands around the western part of the compounds to be quite specific, whereas much structural freedom was found in the eastern part. Vvhile these compounds in general suffered from poor solubility properties, the 4-trifluoromethoxy-phenoxyacetamide western appendage provided a favorable combination of activity and solubility properties. The amine in the eastern appendage, originally required by the pharmacophore model and believed to interact with Asp123 in transmembrane 3 of MCH1R, could be removed without diminishing affinity or functional activity of the compounds. Docking studies suggested that the Asp123 interacts preferentially with the nitrogen of the central quinoline. Synthesis and testing of specific analogues supported our revised binding mode hypothesis.

  DOI：

  10.1021/jm050103y
• 作为产物：
  描述：

  N-(buta-2,3-dien-1-yl)-N-phenylhydroxylamine 在 chloro[1,3-bis(2,6-di-i-propylphenyl)imidazol-2-ylidene]copper(I) 、 氧气 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 10.0h， 生成 4-(4-methylquinolin-2-yl)morpholine
  参考文献：
  名称：

  铜催化的3-N-羟基氨基1,2-丙二烯与醇，硫醇和胺的有氧氧化环化反应生成α-O-，S-和N-取代的4-甲基喹啉衍生物

  摘要：

  描述了通过醇，硫醇和胺与铜催化的N-羟基氨基丙烯的好氧氧化反应，一锅，两步合成α- O-，S-和N-取代的4-甲基喹啉衍生物。该反应顺序涉及N的初始氧化与NuH（Nu = OH，OR，NHR和SR）形成的γ-羟基氨基丙烯形成3个取代的2 en 1 -1，然后由Brønsted酸催化所得产物的分子内环化。我们的机理分析表明，反应是通过自由基类型的机理进行的，而不是通过典型的硝酮中间体途径进行的。这种新的铜催化反应的实用性通过其对几种2-氨基-4-甲基喹啉衍生物的合成的适用性得到了证明，已知这些衍生物是几种生物活性分子的关键前体。

  DOI：

  10.1002/chem.201406317

文献信息

• Copper-Catalyzed Deoxygenative C-2 Amination of Quinoline <i>N</i> -Oxides
  作者：Zhihui Wang、Man-Yi Han、Pinhua Li、Lei Wang

  DOI：10.1002/ejoc.201800963

  日期：2018.11.25

  An unprecedented reaction between quinoline N‐oxides with O‐benzoylhydroxylamines was developed by using CuCl as catalyst, generating deoxygenative products of 2‐aminoquinolines in good yields. 1,2‐Dichloroethane (DCE) as solvent also served as reducing agent to cleave the N–O bond with no additional reductant needed in the reaction.

  通过使用CuCl作为催化剂，喹啉N-氧化物与O-苯甲酰基羟胺之间发生了前所未有的反应，从而以高收率产生了2-氨基喹啉的脱氧产物。1,2-二氯乙烷（DCE）作为溶剂也可以用作还原N-O键的还原剂，而反应中无需其他还原剂。
• Cu-Catalyzed carbamoylation<i>versus</i>amination of quinoline<i>N</i>-oxide with formamides
  作者：Yan Zhang、Shiwei Zhang、Guangxing Xu、Min Li、Chunlei Tang、Weizheng Fan

  DOI：10.1039/c8ob02844c

  日期：——

  An efficient, direct carbamoylation and amination of quinoline N-oxides with formamides to access 2-carbamoyl and 2-amino quinolines has been developed through copper-catalyzed C–C and C–N bond formations via cross-dehydrogenative coupling reactions. The reaction proceeds smoothly over a broad range of substrates with excellent functional group tolerance under mild conditions. Mechanistic studies suggest

  通过铜催化的C-C和C-N键的形成，通过交叉脱氢偶联反应，已开发出一种高效，直接的氨基甲酰基化和喹啉N-氧化物与甲酰胺的胺化反应，以生成2-氨基甲酰基和2-氨基喹啉。在温和条件下，该反应可在广泛的具有良好官能团耐受性的底物上顺利进行。机理研究表明，根据甲酰胺N原子上不同的取代基，在TBHP存在下，该反应是由甲酰胺基或脱羰基氨酰基自由基的形成引发的。
• Robust Acenaphthoimidazolylidene Palladacycles: Highly Efficient Catalysts for the Amination of N-Heteroaryl Chlorides
  作者：Qinyue Deng、Yang Zhang、Haibo Zhu、Tao Tu

  DOI：10.1002/asia.201700877

  日期：2017.9.19

  A series of robust N‐heterocyclic carbene palladacycles have been successfully developed. These showed high catalytic activity and selectivity toward the challenging amination of N‐heteroaryl chlorides. Different primary and secondary amines were fully compatible with this catalytic system. Remarkably, no double amination products could be detected when primary amines were utilized in our catalytic

  已经成功开发了一系列健壮的N杂环卡宾Palladacycles。这些显示出高催化活性和对具有挑战性的N-杂芳基氯化物的选择性。不同的伯胺和仲胺与该催化体系完全相容。值得注意的是，在我们的催化转化中使用伯胺时，没有检测到双胺化产物。此外，该协议已成功扩展到合成罗格列酮，一种用于糖尿病的临床药物，突出了其潜在的药物可行性。
• A Facile Method for Nucleophilic Aromatic Substitution of Cyclic Amine
  作者：Mazaahir Kidwai、Pooja Sapra、Bhavesh Dave

  DOI：10.1080/00397910008087076

  日期：2000.12.1

  Abstract The expeditious solventless nucleophilic aromatic substitution using microwaves is described. A non-conventional synthetic procedure has been developed where basic alumina has been used as energy transfer medium under Microwave Irradiation (MW1). The results were compared with those obtained by the classical method. This rapid and environmentally benign method avoids the use of excess solvents

  摘要 描述了使用微波的快速无溶剂亲核芳香取代。已开发出一种非常规合成程序，其中碱性氧化铝已用作微波辐射 (MW1) 下的能量传输介质。结果与通过经典方法获得的结果进行了比较。这种快速且对环境无害的方法避免了使用过程中通常使用的过量溶剂和有毒碱，使该过程对合成非常有吸引力。
• Oxidative Nickel-Catalyzed <i>ortho</i>-C–H Amination of (Iso)quinolines with Alicyclic Amines Directed by a Sacrificial <i>N</i>-Oxide Group
  作者：Weiqi Zhu、Min Wei、Yanrui Wang、Guo Wang、Jianchun Wang、Honghua Rao

  DOI：10.1021/acs.orglett.3c04193

  日期：2024.2.2

  significant decrease of catalytic reactivity. We herein disclose a nickel-catalyzed and a sacrificial N-oxide group directed oxidative coupling of (iso)quinolyl C–H bonds and alicyclic amines, which furnishes bioimportant amino(iso)quinolines efficiently and selectively in a single step. Noteworthy, this protocol avoids the use of aggressive reactants and very strong bases usually required when aminating

  过渡金属（TM）催化的游离或稠合吡啶（Py）环上的C-H键与游离胺的直接胺化仍然很少，因为胺和Py环往往与许多TM采用非生产性的N键配位，导致催化反应活性显着降低。我们在此公开了镍催化和牺牲N-氧化物基团引导的(异)喹啉基C-H键和脂环胺的氧化偶联，其在一步中有效且选择性地提供生物重要的氨基(异)喹啉。值得注意的是，该方案避免了在非氧化 Py 环上胺化时通常需要使用腐蚀性反应物和非常强的碱。