5-methoxy-1-(4-methoxybenzyl)-1H-indole | 1226219-73-3

• 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: 5-methoxy-1-(4-methoxybenzyl)-1H-indole
• 英文别名: 5-methoxy-1-para-methoxybenzylindole；1-(4 methoxybenzyl)-5-methoxyindole；5-Methoxy-1-[(4-methoxyphenyl)methyl]indole；5-methoxy-1-[(4-methoxyphenyl)methyl]indole
• CAS: 1226219-73-3
• 化学式: C₁₇H₁₇NO₂
• 分子量: 267.327
• InChiKey: XTIBYCMEMDDPFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  23.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-methoxy-1-(4-methoxybenzyl)-1H-indole 在 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 7.5h， 生成 N'-((1-(4-methoxybenzyl)-5-methoxy-1H-indol-3-yl)methylene)-2-(5-bromo-1H-indol-3-yl)-2-oxoacetohydrazide
  参考文献：
  名称：

  Design and synthesis of bis(indolyl)ketohydrazide-hydrazones: Identification of potent and selective novel tubulin inhibitors

  摘要：

  A novel series of ketohydrazide-hydrazones as analogues of naturally occurring coscinamides has been synthesized and evaluated for their anticancer activity against five cancer cell lines. Of the twenty synthesized ketohydrazide-hydrazones, compounds, 21c, 21f, 21g, 21k and 21o showed cytotoxic effects (less than 50% cell survival) against multiple cancer cell lines when tested at a final concentration of 10 mu M. IC50 of three compounds 21f, 21k and 21o was determined to be less than 5 mu M for all tested cancer cell lines. Compound 21k exhibited significant anticancer activity against MCF-7, MDA-MB-231, HCT-116 and JURKAT cancer cell lines with IC50 values of 0.8 mu M, 0.50 mu M, 0.15 mu M, and 0.22 mu M, respectively. Also, 21k was found to be more selectively cytotoxic against tumor cells when compared to normal cells. Preliminary mechanism of action studies indicated that the most active compound 21k induced caspase-dependent apoptosis in cells. 21k arrests cell cycle in G2/M phase by inhibiting of tubulin polymerization (IC50 = 0.6 mu M). (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.04.078
• 作为产物：
  描述：

  5-甲氧基吲哚啉 在 三(五氟苯基)硼烷 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 120.0 ℃ 、10.0 kPa 条件下， 反应 16.0h， 生成 5-methoxy-1-(4-methoxybenzyl)-1H-indole
  参考文献：
  名称：

  沮丧的路易斯对催化二氢吲哚和其他杂环的脱氢氧化

  摘要：

  开发了受挫的路易斯对（FLP）催化的杂环的无受体脱氢。对于N保护的二氢吲哚以及其他四种底物类别，伴随着分子氢的氧化而进行的氧化反应具有很高的收率。通过机理研究，NMR光谱学和X射线晶体分析对反应中间体的表征以及量子力学计算，研究了这种前所未有的FLP催化反应的机理。从氢硼酸铵中间体中释放出的氢是氧化的决定速率的步骤。在第二次催化循环中，加入较弱的路易斯酸作为氢化物穿梭物，使反应速率提高了2.28倍。

  DOI：

  10.1002/anie.201606426

文献信息

• Synthesis of <i>meta</i>-(Indol-3-yl)phenols from Indoles and Cyclohexenone via Palladium(II)-Catalyzed Oxidative Heck Reaction and Dehydrogenative Aromatization in a One-Step Sequence
  作者：Seung Hwan Son、Jeong-Won Shin、Hyuck-Jae Won、Hyung-Seok Yoo、Yang Yil Cho、Soo Lim Kim、Yoon Hu Jang、Boyoung Y. Park、Nam-Jung Kim

  DOI：10.1021/acs.orglett.1c02679

  日期：2021.10.1

  with a wide substrate scope (a total of 25 compounds) via a palladium(II)-catalyzed oxidative Heck reaction and dehydrogenative aromatization in a one-step sequence is reported. This methodology affords a novel route for the privileged structures that are challenging to access via a direct link between indole and phenol, in a highly efficient and atom-economical manner.

  据报道，通过钯 (II) 催化的氧化 Heck 反应和脱氢芳构化以一步顺序轻松构建具有广泛底物范围（总共 25 种化合物）的间-（吲哚-3-基）苯酚骨架。这种方法为通过吲哚和苯酚之间的直接链接以高效和原子经济的方式难以访问的特权结构提供了一种新途径。
• Selective Ruthenium-Catalyzed N-Alkylation of Indoles by Using Alcohols
  作者：Sebastian Bähn、Sebastian Imm、Kathleen Mevius、Lorenz Neubert、Annegret Tillack、Jonathan M. J. Williams、Matthias Beller

  DOI：10.1002/chem.200903144

  日期：2010.3.22

  Alcohols for alkylation! The first homogeneous‐catalyzed N‐alkylations of indoles with aliphatic alcohols proceed under transfer hydrogenation conditions. By the use of the Shvo catalyst and p‐toluenesulfonic acid (PTSA) this atom‐efficient reaction occurs highly selectively with water formed as the only byproduct (see scheme).

  用于烷基化的醇！吲哚与脂肪醇的第一次均相催化N烷基化在转移氢化条件下进行。通过使用Shvo催化剂和对甲苯磺酸（PTSA），该原子效率反应高度选择性地发生，形成的水是唯一的副产物（参见方案）。
• [3 + 2] cycloaddition of 1-(4-Methoxybenzyl)indoles and azaindoles with nitrile oxides
  作者：Reina Kimura、Yoshihiro Sato、Kazuhiro Morisaki、Takahide Nishi

  DOI：10.1016/j.tet.2022.132760

  日期：2022.5

  We studied [3 + 2] cycloaddition reactions of indoles and azaindoles with various nitrile oxides. N-Protection of indoles and azaindoles with the 4-methoxybenzyl group was found to be effective for [3 + 2] cycloaddition with nitrile oxides. Due to the propensity of the nitrile oxides to dimerize, it was necessary to optimize reaction conditions in the case of unstable nitrile oxides. This method was

  我们研究了吲哚和氮杂吲哚与各种腈氧化物的 [3 + 2] 环加成反应。发现具有 4-甲氧基苄基的吲哚和氮杂吲哚的N-保护对于与腈氧化物的 [3 + 2] 环加成是有效的。由于腈氧化物倾向于二聚化，因此有必要在腈氧化物不稳定的情况下优化反应条件。该方法用于合成具有生物活性的3-取代氮杂吲哚衍生物的各种关键中间体。
• Design and synthesis of bis(indolyl)ketohydrazide-hydrazones: Identification of potent and selective novel tubulin inhibitors
  作者：Mukund P. Tantak、Linus Klingler、V. Arun、Anil Kumar、Rachna Sadana、Dalip Kumar

  DOI：10.1016/j.ejmech.2017.04.078

  日期：2017.8

  A novel series of ketohydrazide-hydrazones as analogues of naturally occurring coscinamides has been synthesized and evaluated for their anticancer activity against five cancer cell lines. Of the twenty synthesized ketohydrazide-hydrazones, compounds, 21c, 21f, 21g, 21k and 21o showed cytotoxic effects (less than 50% cell survival) against multiple cancer cell lines when tested at a final concentration of 10 mu M. IC50 of three compounds 21f, 21k and 21o was determined to be less than 5 mu M for all tested cancer cell lines. Compound 21k exhibited significant anticancer activity against MCF-7, MDA-MB-231, HCT-116 and JURKAT cancer cell lines with IC50 values of 0.8 mu M, 0.50 mu M, 0.15 mu M, and 0.22 mu M, respectively. Also, 21k was found to be more selectively cytotoxic against tumor cells when compared to normal cells. Preliminary mechanism of action studies indicated that the most active compound 21k induced caspase-dependent apoptosis in cells. 21k arrests cell cycle in G2/M phase by inhibiting of tubulin polymerization (IC50 = 0.6 mu M). (C) 2017 Elsevier Masson SAS. All rights reserved.
• Frustrated Lewis Pair Catalyzed Dehydrogenative Oxidation of Indolines and Other Heterocycles
  作者：Alexander F. G. Maier、Sebastian Tussing、Tobias Schneider、Ulrich Flörke、Zheng-Wang Qu、Stefan Grimme、Jan Paradies

  DOI：10.1002/anie.201606426

  日期：2016.9.26

  An acceptorless dehydrogenation of heterocycles catalyzed by frustrated Lewis pairs (FLPs) was developed. Oxidation with concomitant liberation of molecular hydrogen proceeded in high to excellent yields for N‐protected indolines as well as four other substrate classes. The mechanism of this unprecedented FLP‐catalyzed reaction was investigated by mechanistic studies, characterization of reaction intermediates

  开发了受挫的路易斯对（FLP）催化的杂环的无受体脱氢。对于N保护的二氢吲哚以及其他四种底物类别，伴随着分子氢的氧化而进行的氧化反应具有很高的收率。通过机理研究，NMR光谱学和X射线晶体分析对反应中间体的表征以及量子力学计算，研究了这种前所未有的FLP催化反应的机理。从氢硼酸铵中间体中释放出的氢是氧化的决定速率的步骤。在第二次催化循环中，加入较弱的路易斯酸作为氢化物穿梭物，使反应速率提高了2.28倍。