1-{3-[2-(dimethylamino)ethyl]-5-[(1H-1,2,4-triazol-1-yl)methyl]-1H-indol-1-yl}ethan-1-one

• 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-{3-[2-(dimethylamino)ethyl]-5-[(1H-1,2,4-triazol-1-yl)methyl]-1H-indol-1-yl}ethan-1-one
• 英文别名: 1-(5-((1H-1,2,4-triazol-1-yl)methyl)-3-(2-(dimethylamino)ethyl)-1H-indol-1-yl)ethan-1-one；1-[3-[2-(Dimethylamino)ethyl]-5-(1,2,4-triazol-1-ylmethyl)indol-1-yl]ethanone
• 化学式: C₁₇H₂₁N₅O
• 分子量: 311.387
• InChiKey: GLUHIRZNOGNIKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  56
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-{3-[2-(dimethylamino)ethyl]-5-[(1H-1,2,4-triazol-1-yl)methyl]-1H-indol-1-yl}ethan-1-one 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以85%的产率得到利扎曲坦
  参考文献：
  名称：

  A New Synthesis of Rizatriptan Based on Radical Cyclization

  摘要：

  已经开发出一种新的方法，适用于制备在3位带有2-(二烷基氨基)-乙基取代基的吲哚衍生物。将这种方法应用于合成N,N-二甲基-2-{5-[(1H-1,2,4-三唑-1-基)甲基]-1H-吲哚-3-基}乙烷-1-胺(利扎曲普坦;3)的描述。关键的反应步骤是基于N-[4-(二甲基氨基)丁-2-炔-1-基]-N-{2-碘-4-[(1H-1,2,4-三唑-1-基)甲基]苯基}乙酰胺(21)的自由基环化，该化合物通过Mannich反应容易获得，随后是对最初形成的甲基亚甲基衍生物22的异构化。

  DOI：

  10.1135/cccc20080116
• 作为产物：
  描述：

  N,N-二甲基色胺 在 三乙基硅烷 、 硫酸 、 溶剂黄146 、 三氟乙酸 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 甲苯 为溶剂， 反应 6.0h， 生成 1-{3-[2-(dimethylamino)ethyl]-5-[(1H-1,2,4-triazol-1-yl)methyl]-1H-indol-1-yl}ethan-1-one
  参考文献：
  名称：

  A novel and convenient route for the construction of 5-((1H-1,2,4-triazol-1-yl)methyl)-1H-indoles and its application in the synthesis of Rizatriptan

  摘要：

  In this study, a novel and convenient route for the construction of 5-((1H-1,2,4-triazol-1-yl)methyl)-1H-indoles (8) is presented starting from (1H-1,2,4-triazol-1-yl)methanol (5) and indolines (6) under 98% H2SO4 at room temperature for 4-24 h, followed by deacetylation and dehydrogenation. Based on this finding, a novel route to synthesize Rizatriptan starting from tryptamine was designed and accomplished with 48.5% overall yield in 6 steps. Compared with operational art, the new route afforded higher yield and more pure products requiring no chromatographic purification, which may further be applied in industrialization. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2014.05.063

文献信息

• Translating Planar Heterocycles into Three‐Dimensional Analogs by Photoinduced Hydrocarboxylation**
  作者：Myriam Mikhael、Sara N. Alektiar、Charles S. Yeung、Zachary K. Wickens

  DOI：10.1002/anie.202303264

  日期：2023.7.24

  We report a new strategy that translates indoles and related heterocycles into diverse 3D analogs by dearomative hydrocarboxylation. The transformation is highly chemoselective, broad in scope, operationally simple, and readily amenable to high-throughput experimentation (HTE).

  我们报告了一种新策略，通过脱芳烃加氢羧化将吲哚和相关杂环化合物转化为多种 3D 类似物。该转化具有高度化学选择性、范围广泛、操作简单且易于进行高通量实验（HTE）。
• A New Synthesis of Rizatriptan Based on Radical Cyclization
  作者：Stanislav Rádl、Ondřej Klecán、Robert Klvaňa、Jaroslav Havlíček

  DOI：10.1135/cccc20080116

  日期：——

  A new methodology useful for preparation of indole derivatives bearing a 2-(dialkylamino)-ethyl substituent at the 3-position has been developed. Application of this methodology to the synthesis of N,N-dimethyl-2-5-[(1H-1,2,4-triazol-1-yl)methyl]-1H-indol-3-yl}ethan-1-amine (rizatriptan; 3) is described. The key reaction step is based on the radical cyclization of N-[4-(dimethylamino)but-2-yn-1-yl]-N-2-iodo-4-[(1H-1,2,4-triazol-1-yl)methyl]phenyl}-acetamide (21), easily available by the Mannich reaction, and subsequent isomerization of the primarily formed methylidene derivative 22.

  已经开发出一种新的方法，适用于制备在3位带有2-(二烷基氨基)-乙基取代基的吲哚衍生物。将这种方法应用于合成N,N-二甲基-2-5-[(1H-1,2,4-三唑-1-基)甲基]-1H-吲哚-3-基}乙烷-1-胺(利扎曲普坦;3)的描述。关键的反应步骤是基于N-[4-(二甲基氨基)丁-2-炔-1-基]-N-2-碘-4-[(1H-1,2,4-三唑-1-基)甲基]苯基}乙酰胺(21)的自由基环化，该化合物通过Mannich反应容易获得，随后是对最初形成的甲基亚甲基衍生物22的异构化。

• A novel and convenient route for the construction of 5-((1H-1,2,4-triazol-1-yl)methyl)-1H-indoles and its application in the synthesis of Rizatriptan
  作者：Yi He、Xiaolong Li、Jue Li、Xiaocen Li、Li Guo、Li Hai、Yong Wu

  DOI：10.1016/j.tetlet.2014.05.063

  日期：2014.7

  In this study, a novel and convenient route for the construction of 5-((1H-1,2,4-triazol-1-yl)methyl)-1H-indoles (8) is presented starting from (1H-1,2,4-triazol-1-yl)methanol (5) and indolines (6) under 98% H2SO4 at room temperature for 4-24 h, followed by deacetylation and dehydrogenation. Based on this finding, a novel route to synthesize Rizatriptan starting from tryptamine was designed and accomplished with 48.5% overall yield in 6 steps. Compared with operational art, the new route afforded higher yield and more pure products requiring no chromatographic purification, which may further be applied in industrialization. (C) 2014 Elsevier Ltd. All rights reserved.