9-(difluoromethyl)-9H-pyrido[2,3-b]indole-3-carbaldehyde | 1603830-67-6

• 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: 9-(difluoromethyl)-9H-pyrido[2,3-b]indole-3-carbaldehyde
• 英文别名: 9-(Difluoromethyl)pyrido[2,3-b]indole-3-carbaldehyde
• CAS: 1603830-67-6
• 化学式: C₁₃H₈F₂N₂O
• 分子量: 246.216
• InChiKey: OKAWNESKFBHWCN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  9-(difluoromethyl)-9H-pyrido[2,3-b]indole-3-carbaldehyde 、 甲基三苯基溴化膦 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以37%的产率得到9-(difluoromethyl)-3-ethenyl-9H-pyrido[2,3-b]indole
  参考文献：
  名称：

  Design, synthesis and pharmacological evaluation of novel polycyclic heteroarene ethers as PDE10A inhibitors: Part I

  摘要：

  We report analogue-based rational design and synthesis of two novel series of polycyclic heteroarenes, pyrrolo[3,2-b]quinolines and pyrido[2,3-b]indoles, tethered to a biaryl system by a methyl-, ethyl-or propyl ether as PDE10A inhibitors. A number of analogues were prepared with variable chain length and evaluated for their ability to block PDE10A enzyme using a radiometric assay. Detailed SAR analyses revealed that compounds with an ethyl ether linker are superior in potency compared to compounds with methyl or propyl ether linkers. These compounds, in general, showed poor metabolic stability in rat and human liver microsomes. The metabolic profile of one of the potent compounds was studied in detail to identify metabolic liabilities of these compounds. Structural modifications were carried out that resulted in improved metabolic stability without significant loss of potency. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.054
• 作为产物：
  描述：

  2-氨基-3-溴-5-氰基吡啶 在 tris-(dibenzylideneacetone)dipalladium(0) 、 palladium diacetate 、 二异丁基氢化铝 、 特戊酸钠 、 potassium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 11.0h， 生成 9-(difluoromethyl)-9H-pyrido[2,3-b]indole-3-carbaldehyde
  参考文献：
  名称：

  Design, synthesis and pharmacological evaluation of novel polycyclic heteroarene ethers as PDE10A inhibitors: Part I

  摘要：

  We report analogue-based rational design and synthesis of two novel series of polycyclic heteroarenes, pyrrolo[3,2-b]quinolines and pyrido[2,3-b]indoles, tethered to a biaryl system by a methyl-, ethyl-or propyl ether as PDE10A inhibitors. A number of analogues were prepared with variable chain length and evaluated for their ability to block PDE10A enzyme using a radiometric assay. Detailed SAR analyses revealed that compounds with an ethyl ether linker are superior in potency compared to compounds with methyl or propyl ether linkers. These compounds, in general, showed poor metabolic stability in rat and human liver microsomes. The metabolic profile of one of the potent compounds was studied in detail to identify metabolic liabilities of these compounds. Structural modifications were carried out that resulted in improved metabolic stability without significant loss of potency. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.054

文献信息

• <scp>Base‐Promoted</scp> Formylation and <scp> <i>N</i> ‐Difluoromethylation </scp> of Azaindoles with Ethyl Bromodifluoroacetate as a Carbon Source
  作者：Yang Li、Ning Sun、Cai‐Lin Zhang、Meng Hao

  DOI：10.1002/cjoc.202100008

  日期：2021.6

  We reported for the first time that ethyl bromodifluoroacetate directly reacts with azaindole without transition metal catalysis to produce a difluoromethyl protected 5-aldehyde group product in one step. It is worth mentioning that the reacted aldehyde group is only formed at the 5 position. In addition, this method has good substrate applicability and functional group tolerance. Finally, we also

  我们首次报道了溴二氟乙酸乙酯在没有过渡金属催化的情况下直接与氮杂吲哚反应以一步生成二氟甲基保护的5-醛基产物。值得一提的是，已反应的醛基仅在5位上形成。另外，该方法具有良好的底物适用性和官能团耐受性。最后，我们还进行了一些机理辅助实验，证实了醛基碳来自溴二氟乙酸乙酯。