N2,N6-Dicyclohexylpyridine-2,6-dicarboxamide | 126230-12-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N2,N6-Dicyclohexylpyridine-2,6-dicarboxamide
• 英文别名: 2-N,6-N-dicyclohexylpyridine-2,6-dicarboxamide
• CAS: 126230-12-4
• 化学式: C₁₉H₂₇N₃O₂
• mdl: MFCD02046999
• 分子量: 329.442
• InChiKey: ATVTZJWWBXJZFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  71.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  吡啶-2,6-二甲酸 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 12.0h， 生成 N2,N6-Dicyclohexylpyridine-2,6-dicarboxamide
  参考文献：
  名称：

  [EN] MOLECULAR EDITING OF MULTIPLE C-H BONDS BY LEVERAGING RECOGNITION OF DISTANCE, GEOMETRY AND CHIRALITY
  [FR] ÉDITION MOLÉCULAIRE DE LIAISONS C-H MULTIPLES PAR EXPLOITATION DE LA RECONNAISSANCE DE LA DISTANCE, DE LA GÉOMÉTRIE ET DE LA CHIRALITÉ

  摘要：

  This disclosure provides functional templates that direct Pd to functionalize multiple C-H bonds in polycyclic aza-arenes such as quinolines and related heterocycles at locations that are difficult to isolate and reach for substitution. Herein disclosed are two conceptually distinct directing templates (T) that enable site- selective C6 and C7-H activation of polycyclic aza-arenes. These catalytic pyridine-based templates recruit the aza-arene substrate throughN-coordination, enabling the directing arm to deliver the catalyst and precisely activate remote and adjacent C6 or C7-H bond (Fig. 1d). In parallel, we discovered that the use of a simple and readily prepared template chaperone (TC) can turn over the directing template, allowing it to be used catalytically for the first time. Notably, chiral recognition is vital in the granular discrimination between competing C3 and C7-H bonds when the differentiation via distance and geometry is insufficient. Thus, precise recognition of a directing template's distance, geometry and chirality now enables the iterative C-H editing of quinoline and related pharmacophores at any desired site and order. The methods disclosed herein can also be used for diverse and late-stage modification of heterocycle-based drug molecules and pharmacophores.

  公开号：

  WO2023212565A2
• 作为试剂：
  描述：

  喹啉 、 (2-溴乙炔基)三异丙基硅烷 在 palladium diacetate 、 N₂-(2,6-Dimethoxyphenyl)-N₆-(8-(pyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-2-yl)pyridine-2,6-dicarboxamide 、 N2,N6-Dicyclohexylpyridine-2,6-dicarboxamide 、 水 、 copper hydroxide 、 silver carbonate 、 N-乙酰甘氨酸 、 4-二甲氨基吡啶 作用下， 以 乙腈 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 以66%的产率得到6-((triisopropylsilyl)ethynyl)quinoline
  参考文献：
  名称：

  通过距离、几何形状和手性对氮杂芳烃 C-H 键进行分子编辑

  摘要：

  通过连续选择性 C-H 功能化对杂芳烃碳-氢 (C-H) 键进行直接分子编辑，有可能快速进入不同的化学空间；药物化学领域一项有价值但往往具有挑战性的事业1。与电子偏向杂环 C-H 键2-9相比，双环氮杂芳烃上的远程苯并环 C-H 键由于缺乏内在的空间/电子偏向而特别难以区分10-12。我们在此报告了两种概念上不同的定向模板，通过仔细调节距离、几何形状和先前未考虑的因素，能够对双环氮杂芳烃上相邻的远程位置（C6与C7）和位置相似的位置（C3与C7）进行模块化区分和功能化模板设计中的手性。该策略能够在存在与 C7 空间相似的竞争性 C3 位置的情况下，在喹啉的相邻 C6 和 C7 位置上进行直接 C-H 烯化、炔基化和烯丙基化。值得注意的是，含喹啉药效团的这种位点选择性、迭代和后期 C-H 编辑可以以不同的顺序模块化执行，以适应定制的合成应用。该报告结合之前报道的补充方法，现在完全建立了统一的

  DOI：

  10.1038/s41586-022-05175-1

文献信息

• Facile Preparation of 6-Bromopyridine-2-carboxamide and Pyridine-2,6-dicarboxamide: Partial Aminocarbonylation of 2,6-Dibromopyridine
  作者：Hiroshi Horino、Hiroyuki Sakaba、Mannosuke Arai

  DOI：10.1055/s-1989-27372

  日期：——

  The palladium-catalyzed carbonylation of 2,6-dibromopyridine in the presence of primary amines under controlled conditions (carbon monoxide pressure) gives mainly N-aryl- or N-alkyl-6-bromopyridine-2-carboxamides accompanied by N,N′-diaryl- or N,N′-dialkylpyridine- 2,6-dicarboxamides. Further aminocarbonylation of the N-aryl- and N- alkyl-6-bromopyridine-2-carboxamides affords unsymmetric N,N′- diaryl, N-alkyl-N′-aryl-, or N,N′-dialkylpyridine-2,6-dicarboxamides.

  在受控条件下（如一氧化碳压力）下，钯催化的2,6-二溴吡啶与初级胺的羰基化反应主要生成N-芳基或N-烷基-6-溴吡啶-2-羧酰胺，并伴有N,N′-二芳基或N,N′-二烷基吡啶-2,6-二羧酰胺。对N-芳基和N-烷基-6-溴吡啶-2-羧酰胺进行进一步的氨基羰基化反应，可以得到不对称的N,N′-二芳基、N-烷基-N′-芳基或N,N′-二烷基吡啶-2,6-二羧酰胺。
• HORINO, HIROSHI;SAKABA, HIROYUKI;ARAI, MANNOSUKE, SYNTHESIS,(1989) N, C. 715-718
  作者：HORINO, HIROSHI、SAKABA, HIROYUKI、ARAI, MANNOSUKE

  DOI：——

  日期：——
• COMPOUNDS FOR USE IN TREATMENT OF MUCOSITIS
  申请人：Cellceutix Corporation

  公开号：EP2709619B1

  公开（公告）日：2017-10-11
• KR2023/5049
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] MOLECULAR EDITING OF MULTIPLE C-H BONDS BY LEVERAGING RECOGNITION OF DISTANCE, GEOMETRY AND CHIRALITY<br/>[FR] ÉDITION MOLÉCULAIRE DE LIAISONS C-H MULTIPLES PAR EXPLOITATION DE LA RECONNAISSANCE DE LA DISTANCE, DE LA GÉOMÉTRIE ET DE LA CHIRALITÉ
  申请人：[en]THE SCRIPPS RESEARCH INSTITUTE

  公开号：WO2023212565A2

  公开（公告）日：2023-11-02

  This disclosure provides functional templates that direct Pd to functionalize multiple C-H bonds in polycyclic aza-arenes such as quinolines and related heterocycles at locations that are difficult to isolate and reach for substitution. Herein disclosed are two conceptually distinct directing templates (T) that enable site- selective C6 and C7-H activation of polycyclic aza-arenes. These catalytic pyridine-based templates recruit the aza-arene substrate throughN-coordination, enabling the directing arm to deliver the catalyst and precisely activate remote and adjacent C6 or C7-H bond (Fig. 1d). In parallel, we discovered that the use of a simple and readily prepared template chaperone (TC) can turn over the directing template, allowing it to be used catalytically for the first time. Notably, chiral recognition is vital in the granular discrimination between competing C3 and C7-H bonds when the differentiation via distance and geometry is insufficient. Thus, precise recognition of a directing template's distance, geometry and chirality now enables the iterative C-H editing of quinoline and related pharmacophores at any desired site and order. The methods disclosed herein can also be used for diverse and late-stage modification of heterocycle-based drug molecules and pharmacophores.