N,N-diallyl-2-(1H-indol-3-yl)-2-oxoacetamide | 1174656-44-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N,N-diallyl-2-(1H-indol-3-yl)-2-oxoacetamide
• 英文别名: 2-(1H-indol-3-yl)-2-oxo-N,N-bis(prop-2-enyl)acetamide
• CAS: 1174656-44-0
• 化学式: C₁₆H₁₆N₂O₂
• 分子量: 268.315
• InChiKey: GTBFUWIEABOTTL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  53.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N,N-diallyl-2-(1H-indol-3-yl)-2-oxoacetamide 在 lithium aluminium deuteride 作用下， 以 四氢呋喃 为溶剂， 以70%的产率得到N,N-diallyl-[α,α,β,β-d4]-tryptamine
  参考文献：
  名称：

  Microwave-accelerated synthesis of psychoactive deuteratedN,N-dialkylated-[α,α,β,β-d₄]-tryptamines

  摘要：

  已知大量N,N-二烷基色胺对人类具有精神活性效应。这使得其在临床和法医领域受到越来越多的关注。氘代色胺非常适合用作MS生物分析过程中的内标，或在生物化学NMR研究中使用。本研究报告了一种通过锂铝氘化物还原甘油醛酰胺前体（Speeter和Anthony法获得）合成22种N,N-二烷基-[α,α,β,β-d4]-色胺的微波促进合成方法。合成在单模系统中进行，高温高压条件下使用无水四氢呋喃作为溶剂，温度为150°C。5分钟内即可获得良好的产率。版权所有 © 2008 John Wiley & Sons, Ltd.

  DOI：

  10.1002/jlcr.1557
• 作为产物：
  描述：

  吲哚 以 四氢呋喃 、 乙醚 为溶剂， 反应 8.0h， 生成 N,N-diallyl-2-(1H-indol-3-yl)-2-oxoacetamide
  参考文献：
  名称：

  Receptor binding profiles and quantitative structure–affinity relationships of some 5-substituted- N , N -diallyltryptamines

  摘要：

  N,N-Diallyltryptamine (DALT) and 5-methoxy-N,N-diallyltryptamine (5-MeO-DALT) are two tryptamines synthesized and tested by Alexander Shulgin. In self-experiments, 5-MeO-DALT was reported to be psychoactive in the 12-20 mg range, while the unsubstituted compound DALT had few discernible effects in the 42-80 mg range. Recently, 5-MeO-DALT has been used in nonmedical settings for its psychoactive effects, but these effects have been poorly characterized and little is known of its pharmacological properties. We extended the work of Shulgin by synthesizing additional 5-substituted-DALTs. We then compared them to DALT and 5-MeO-DALT for their binding affinities at 45 cloned receptors and transporter proteins. Based on in vitro binding affinity, we identified 27 potential receptor targets for the 5-substituted- DALT compounds. Five of the DALT compounds had affinity in the 10-80 nM range for serotonin 5-HT1A and 5-HT2B receptors, while the affinity of DALT itself at 5-HT1A receptors was slightly lower at 100 nM. Among the 5-HT2 subtypes, the weakest affinity was at 5-HT2A receptors, spanning 250-730 nM. Five of the DALT compounds had affinity in the 50-400 nM range for serotonin 5-HT1D, 5-HT6, and 5-HT7 receptors; again, it was the unsubstituted DALT that had the weakest affinity at all three subtypes. The test drugs had even weaker affinity for 5-HT1B, 5-HT1E, and 5-HT5A subtypes and little or no affinity for the 5-HT3 subtype. These compounds also had generally nanomolar affinities for adrenergic alpha(2A), alpha(2B), and alpha(2C) receptors, sigma receptors sigma(1) and sigma(2), histamine H-1 receptors, and norepinephrine and serotonin uptake transporters. They also bound to other targets in the nanomolar-to-low micromolar range. Based on these binding results, it is likely that multiple serotonin receptors, as well as several non-serotonergic sites are important for the psychoactive effects of DALT drugs. To learn whether any quantitative structure-affinity relationships existed, we evaluated correlations among physicochemical properties of the congeneric 5-substituted-DALT compounds. The descriptors included electronic (sigma(p)), hydrophobic (pi), and steric (CMR) parameters. The binding affinity at 5-HT1A, 5-HT1D, 5-HT7, and kappa opioid receptors was positively correlated with the steric volume parameter CMR. At alpha(2A), alpha(2B), and alpha(2C) receptors, and at the histamine H-1 receptor, binding affinity was correlated with the Hammett substituent parameter sigma(p); higher affinity was associated with larger sigma(p) values. At the sigma(2) receptor, higher affinity was correlated with increasing p. These correlations should aid in the development of more potent and selective drugs within this family of compounds. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.12.053

文献信息

• Large‐Scale Synthesis of a Niche Olefin Metathesis Catalyst Bearing an Unsymmetrical N‐Heterocyclic Carbene (NHC) Ligand and its Application in a Green Pharmaceutical Context
  作者：Tomasz Nienałtowski、Paweł Szczepanik、Paweł Małecki、Dorota Czajkowska‐Szczykowska、Stefan Czarnocki、Jolanta Pawłowska、Anna Kajetanowicz、Karol Grela

  DOI：10.1002/chem.202003830

  日期：2020.12

  large‐scale synthesis of known Ru olefin metathesis catalyst VII featuring an unsymmetrical N‐heterocyclic carbene (NHC) ligand with one 2,5‐diisopropylphenyl (DIPP) and one thiophenylmethylene N‐substituent is reported. The optimised procedure does not require column chromatography in any step and allows for preparation of up to 0.5 kg batches of the catalyst from simple precursors. The application profile

  据报道大规模合成了已知的钌烯烃复分解催化剂VII，该催化剂具有一个不对称的N-杂环卡宾（NHC）配体，其中有一个2,5-二异丙基苯基（DIPP）和一个硫代苯基亚甲基N取代基。优化的程序在任何步骤都不需要柱色谱，并且可以从简单的前体中制备多达0.5 kg批次的催化剂。在环保型碳酸二甲酯（DMC）中研究了所得催化剂的应用概况。虽然七在与缺乏电子的配偶的交叉复分解（CM）中显示出低效率，对于具有容易使C-C双键异构化的底物，其结果达到了良好至优异的结果。这包括具有药用化学意义的多功能底物，例如精神活性5F‐PB‐22和NM‐2201的类似物以及两种PDE5抑制剂西地那非和伐地那非。最后，在DMC中对Vardenafil衍生物进行了较大规模的闭环复分解（RCM），从而以高收率和低Ru污染水平（7.7 ppm）直接分离了预期的产物（23 g）。
• Ruthenium Catalysts Supported by Amino-Substituted N-Heterocyclic Carbene Ligands for Olefin Metathesis of Challenging Substrates
  作者：Vincent César、Yin Zhang、Wioletta Kośnik、Adam Zieliński、Adam A. Rajkiewicz、Mirko Ruamps、Stéphanie Bastin、Noël Lugan、Guy Lavigne、Karol Grela

  DOI：10.1002/chem.201604934

  日期：2017.2.3

  well‐known IMes ligand by substituting the carbenic heterocycle with one and two dimethylamino groups, respectively, were employed for the synthesis of second‐generation Grubbs‐ and Grubbs–Hoveyda‐type ruthenium metathesis precatalysts. Whereas the stability of the complexes was found to depend on the degree of dimethylamino‐substitution and on the type of complex, the backbone‐substitution was shown to

  N-杂环卡宾（NHC）配体IMes和IMes通过分别用一个和两个二甲基氨基取代羧基杂环而从著名的IMes配体衍生而来，用于合成第二代Grubbs和Grubbs-Hoveyda型钌复分解前催化剂。尽管发现复合物的稳定性取决于二甲基氨基取代的程度和复合物的类型，但骨架取代显示出对它们在闭环复分解反应中的催化活性有积极影响，其作用更为明显。在第二代Grubbs型系列中。新的配合物已成功用于许多具有挑战性的烯烃复分解反应中，导致形成四取代的C = C双键和/或官能化的化合物。
• Ethyl Lactate: A Green Solvent for Olefin Metathesis
  作者：Sebastian Planer、Anupam Jana、Karol Grela

  DOI：10.1002/cssc.201901735

  日期：2019.10.21

  with ethyl lactate as solvent was evaluated using a range of substrates and conditions. In addition, the preparation of a metathesis catalyst in simplified manner by using the advantages of ethyl lactate was accomplished. The application of ethyl lactate facilitates product isolation (also allowing for lower ruthenium contamination in crude metathesis products) and improves the overall green angle

  使用一定范围的底物和条件，评估了所选的市售钌烯烃复分解催化剂与乳酸乙酯作为溶剂的相容性。另外，利用乳酸乙酯的优点以简化的方式完成了复分解催化剂的制备。乳酸乙酯的应用促进了产物的分离（还使粗复分解产物中的钌污染降低了），并改善了烯烃复分解的整体生角。
• Electrochemical oxidative N–H/P–H cross-coupling with H₂ evolution towards the synthesis of tertiary phosphines
  作者：Yong Yuan、Xue Liu、Jingcheng Hu、Pengjie Wang、Shengchun Wang、Hesham Alhumade、Aiwen Lei

  DOI：10.1039/d1sc07248j

  日期：——

  Tertiary phosphines(III) find widespread use in many aspects of synthetic organic chemistry. Herein, we developed a facile and novel electrochemical oxidative N–H/P–H cross-coupling method, leading to a series of expected tertiary phosphines(III) under mild conditions with excellent yields. It is worth noting that this electrochemical protocol features very good reaction selectivity, where only a 1 : 1

  叔膦( III )在合成有机化学的许多方面都有广泛的用途。在此，我们开发了一种简便且新颖的电化学氧化N-H/P-H交叉偶联方法，在温和的条件下以优异的产率产生了一系列预期的叔膦( III )。值得注意的是，该电化学方案具有非常好的反应选择性，反应中仅需要胺和磷化氢的比例为1:1。此外，该电化学协议被证明是实用且可扩展的。机理分析表明 P 自由基参与了该反应。
• Receptor binding profiles and quantitative structure–affinity relationships of some 5-substituted- N , N -diallyltryptamines
  作者：Nicholas V. Cozzi、Paul F. Daley

  DOI：10.1016/j.bmcl.2015.12.053

  日期：2016.2

  N,N-Diallyltryptamine (DALT) and 5-methoxy-N,N-diallyltryptamine (5-MeO-DALT) are two tryptamines synthesized and tested by Alexander Shulgin. In self-experiments, 5-MeO-DALT was reported to be psychoactive in the 12-20 mg range, while the unsubstituted compound DALT had few discernible effects in the 42-80 mg range. Recently, 5-MeO-DALT has been used in nonmedical settings for its psychoactive effects, but these effects have been poorly characterized and little is known of its pharmacological properties. We extended the work of Shulgin by synthesizing additional 5-substituted-DALTs. We then compared them to DALT and 5-MeO-DALT for their binding affinities at 45 cloned receptors and transporter proteins. Based on in vitro binding affinity, we identified 27 potential receptor targets for the 5-substituted- DALT compounds. Five of the DALT compounds had affinity in the 10-80 nM range for serotonin 5-HT1A and 5-HT2B receptors, while the affinity of DALT itself at 5-HT1A receptors was slightly lower at 100 nM. Among the 5-HT2 subtypes, the weakest affinity was at 5-HT2A receptors, spanning 250-730 nM. Five of the DALT compounds had affinity in the 50-400 nM range for serotonin 5-HT1D, 5-HT6, and 5-HT7 receptors; again, it was the unsubstituted DALT that had the weakest affinity at all three subtypes. The test drugs had even weaker affinity for 5-HT1B, 5-HT1E, and 5-HT5A subtypes and little or no affinity for the 5-HT3 subtype. These compounds also had generally nanomolar affinities for adrenergic alpha(2A), alpha(2B), and alpha(2C) receptors, sigma receptors sigma(1) and sigma(2), histamine H-1 receptors, and norepinephrine and serotonin uptake transporters. They also bound to other targets in the nanomolar-to-low micromolar range. Based on these binding results, it is likely that multiple serotonin receptors, as well as several non-serotonergic sites are important for the psychoactive effects of DALT drugs. To learn whether any quantitative structure-affinity relationships existed, we evaluated correlations among physicochemical properties of the congeneric 5-substituted-DALT compounds. The descriptors included electronic (sigma(p)), hydrophobic (pi), and steric (CMR) parameters. The binding affinity at 5-HT1A, 5-HT1D, 5-HT7, and kappa opioid receptors was positively correlated with the steric volume parameter CMR. At alpha(2A), alpha(2B), and alpha(2C) receptors, and at the histamine H-1 receptor, binding affinity was correlated with the Hammett substituent parameter sigma(p); higher affinity was associated with larger sigma(p) values. At the sigma(2) receptor, higher affinity was correlated with increasing p. These correlations should aid in the development of more potent and selective drugs within this family of compounds. (C) 2015 Elsevier Ltd. All rights reserved.