1-methyl-5-nitro-1H-indole-3-carbonitrile

• 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: 1-methyl-5-nitro-1H-indole-3-carbonitrile
• 英文别名: 1-methyl-5-nitroindole-3-carbonitrile
• 化学式: C₁₀H₇N₃O₂
• 分子量: 201.184
• InChiKey: NONOWDPZWAYNPJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  74.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-methyl-5-nitro-1H-indole-3-carbonitrile 在 palladium on activated charcoal 盐酸 、 硼烷 、 氢气 作用下， 反应 24.0h， 生成 2'-(5-amino-1-methyl-1H-indol-3-yl)spiro(1-azabicyclo<2.2.2>octane-3,5'(4'H)-oxazole) trihydrochloride
  参考文献：
  名称：

  Novel 5-HT3 antagonists: indol-3-ylspiro(azabicycloalkane-3,5'(4'H)oxazoles)

  摘要：

  The synthesis and biochemical evaluation of a series of spirofused indole oxazoline 5-HT3 antagonists is described in which the oxazoline ring acts as a bioisosteric replacement for esters and amides. The effect of substitution about the indole ring has shown the steric limitations of the aromatic binding site. Incorporation of a variety of azabicyclic systems within the rigid spirofused framework has allowed the definition of a binding model which incorporates a number of known antagonists and agonists. In this model steric constraints limit substitution around the indole ring although there is some bulk tolerance at the 1- and 2-positions. The importance of constraining the basic nitrogen within an azabicyclic system is underlined by comparison with the monocyclic piperidine. The highest affinity was observed for those compounds in which the basic nitrogen occupies a bridgehead position, the most potent analogue in this group being the azabicyclic [3.3.1] system (pIC50 = 8.95), suggesting lipophilic interactions may play a role in increasing affinity. A suggested model for agonist binding is included in which the basic nitrogens are superimposed and the 5-hydroxyl group of 5-HT is superimposed on the H-bond-accepting atom of the heterocyclic linking group.

  DOI：

  10.1021/jm00084a007
• 作为产物：
  描述：

  5-硝基吲哚 在 2,2'-联吡啶 、 氧气 、 palladium diacetate 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.75h， 生成 1-methyl-5-nitro-1H-indole-3-carbonitrile
  参考文献：
  名称：

  钯催化芳基腈的定向碳-碳键活化用于氰基转移

  摘要：

  在此，我们报道了使用芳基腈作为氰基源，通过钯催化的定向 C-CN 活化反应进行吲哚的 C-H 氰化。苯氧基取向基团的使用是C-CN键断裂的关键。该方案具有底物范围广、效率高、区域选择性高的特点。此外，该方案的实际应用在吲哚衍生物的后期功能化和合成中得到了展示，吲哚衍生物是通过氰化过程衍生自药物和天然产物。

  DOI：

  10.1021/acs.orglett.4c00429

文献信息

• Cyanation of indoles with benzyl cyanide as the cyanide anion surrogate
  作者：Lianpeng Zhang、Qiaodong Wen、Jisong Jin、Chen Wang、Ping Lu、Yanguang Wang

  DOI：10.1016/j.tet.2013.03.089

  日期：2013.5

  A copper-mediated direct cyanation of indoles with benzyl cyanide as the cyanide anion surrogate has been achieved. The cascade reaction furnished 3-cyanoindoles under mild reaction conditions in good to excellent yields with various functional groups tolerance.

  已经实现了用苄基氰化物作为氰化物阴离子替代物对吲哚进行铜介导的直接氰化。该级联反应在温和的反应条件下提供了3-氰基吲哚，具有良好的收率和优异的产率，并具有各种官能团耐受性。
• 一种选择性钠通道调节剂及其制备和应用
  申请人：明慧医药（上海）有限公司

  公开号：CN112300051A

  公开（公告）日：2021-02-02

  本发明提供了作为选择性钠通道调节剂的化合物及合成和使用方法，具体地，本发明提供了一种如式(I)所示的化合物，及其制备方法和作为选择性钠通道调节剂的用途。所述的化合物表现出作为钠通道调节剂的优异活性。
• Aerobic Copper-Promoted Radical-Type Cleavage of Coordinated Cyanide Anion: Nitrogen Transfer to Aldehydes To Form Nitriles
  作者：Qian Wu、Yi Luo、Aiwen Lei、Jingsong You

  DOI：10.1021/jacs.5b10945

  日期：2016.3.9

  coordinated cyanide anion under a dioxygen atmosphere, which enables a nitrogen transfer to various aldehydes. Mechanistic study of this unprecedented transformation suggests that the single electron-transfer process could be involved in the overall course. This protocol provides a new cleavage pattern for the cyanide ion and would eventually lead to a more useful synthetic pathway to nitriles from aldehydes

  我们首次公开了在双氧气氛下铜促进的 C≡N 三键裂解配位氰化物阴离子，这使得氮转移到各种醛。对这种前所未有的转变的机理研究表明，整个过程可能涉及单个电子转移过程。该协议为氰化物离子提供了一种新的裂解模式，并最终会导致一条更有用的合成途径，从醛到腈。
• Copper-mediated cyanation of indoles and electron-rich arenes using DMF as a single surrogate
  作者：Lianpeng Zhang、Ping Lu、Yanguang Wang

  DOI：10.1039/c5ob01244a

  日期：——

  The copper-mediated cyanation of indoles with DMF as a single surrogate of “CN” has been realized.

  吲哚的铜介导氰化反应中，使用DMF作为“CN”的单一替代试剂已经实现。
• The palladium-catalyzed cyanation of indole C–H bonds with the combination of NH4HCO3 and DMSO as a safe cyanide source
  作者：Xinyi Ren、Jianbin Chen、Fan Chen、Jiang Cheng

  DOI：10.1039/c1cc11603g

  日期：——

  A palladium-catalyzed cyanation of the 3-position of indole sp2 C–H bonds by the combination of NH4HCO3 and DMSO as the “CN” source was achieved to provide aromatic nitriles in moderate to good yields with excellent regioselectivity. It represents a practical and safe cyanation method.

  实现了通过NH4HCO3和DMSO组合作为“CN”源，钯催化的吲哚3-位sp2 C–H键的氰化反应，以中等至良好的产率得到了具有优异区域选择性的芳香腈。这代表了一种实用且安全的氰化方法。