1-[(3-Bromophenyl)methoxy]-2-chloro-4-nitrobenzene | 1002471-58-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-[(3-Bromophenyl)methoxy]-2-chloro-4-nitrobenzene
• CAS: 1002471-58-0
• 化学式: C₁₃H₉BrClNO₃
• mdl: MFCD10709174
• 分子量: 342.576
• InChiKey: VJTHGAOKRLLSAI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.076
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-[(3-Bromophenyl)methoxy]-2-chloro-4-nitrobenzene 在 氯化铵 、 锌 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 N-[4-[(3-bromophenyl)methoxy]-3-chlorophenyl]-6-(4-morpholin-4-ylsulfonylphenyl)quinazolin-4-amine;hydrochloride
  参考文献：
  名称：

  Kinase Scaffold Repurposing for Neglected Disease Drug Discovery: Discovery of an Efficacious, Lapatanib-Derived Lead Compound for Trypanosomiasis

  摘要：

  Human African trypanosomiasis (HAT) is a neglected tropical disease caused by the protozoan parasite Trypanosoma brucei. Because drugs in use against HAT are toxic and require intravenous dosing, new drugs are needed. Initiating lead discovery campaigns by using chemical scaffolds from drugs approved for other indications can speed up drug discovery for neglected diseases. We demonstrated recently that the 4-anilinoquinazolines lapatinib (GW572016, 1) and canertinib (CI-1033) kill T. brucei with low micromolar EC50 values. We now report promising activity of analogues of 1, which provided an excellent starting point for optimization of the chemotype. Our compound optimization that has led to synthesis of several potent 4-anilinoquinazolines, including NEU617, 23a, a highly potent, orally bioavailable inhibitor of trypanosome replication. At the cellular level, 23a blocks duplication of the kinetoplast and arrests cytokinesis, making it a new chemical tool for studying regulation of the trypanosome cell cycle.

  DOI：

  10.1021/jm400349k
• 作为产物：
  描述：

  2-氯-4-硝基苯酚 、 3-溴苄溴 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 12.0h， 生成 1-[(3-Bromophenyl)methoxy]-2-chloro-4-nitrobenzene
  参考文献：
  名称：

  Kinase Scaffold Repurposing for Neglected Disease Drug Discovery: Discovery of an Efficacious, Lapatanib-Derived Lead Compound for Trypanosomiasis

  摘要：

  Human African trypanosomiasis (HAT) is a neglected tropical disease caused by the protozoan parasite Trypanosoma brucei. Because drugs in use against HAT are toxic and require intravenous dosing, new drugs are needed. Initiating lead discovery campaigns by using chemical scaffolds from drugs approved for other indications can speed up drug discovery for neglected diseases. We demonstrated recently that the 4-anilinoquinazolines lapatinib (GW572016, 1) and canertinib (CI-1033) kill T. brucei with low micromolar EC50 values. We now report promising activity of analogues of 1, which provided an excellent starting point for optimization of the chemotype. Our compound optimization that has led to synthesis of several potent 4-anilinoquinazolines, including NEU617, 23a, a highly potent, orally bioavailable inhibitor of trypanosome replication. At the cellular level, 23a blocks duplication of the kinetoplast and arrests cytokinesis, making it a new chemical tool for studying regulation of the trypanosome cell cycle.

  DOI：

  10.1021/jm400349k

文献信息

• Palladium‐Catalyzed Aminocarbonylation of Aryl Halides with <i>N</i> , <i>N</i> ‐Dialkylformamide Acetals
  作者：Shuichi Hirata、Takao Osako、Yasuhiro Uozumi

  DOI：10.1002/hlca.202100162

  日期：2021.11

  We developed a protocol for the palladium-catalyzed aminocarbonylation of aryl halides using less-toxic formamide acetals as bench-stable aminocarbonyl sources under neutral conditions. Various aryl (including heteroaryl) halides reacted with N,N-dialkylformamide acetals in the presence of a catalytic amount of tris(dibenzylideneacetone)dipalladium(0)-chloroform adduct and xantphos to give the corresponding

  我们开发了一种在中性条件下使用毒性较低的甲酰胺缩醛作为实验室稳定的氨基羰基来源的芳基卤化物的钯催化氨基羰基化的协议。在催化量的三（二亚苄基丙酮）二钯（0）-氯仿存在下，各种芳基（包括杂芳基）卤化物与N , N - 二烷基甲酰胺缩醛反应加合物和黄磷在 90–140 °C 下生成相应的芳族甲酰胺，无需任何活化剂或碱，化学产率高达定量。该方案适用于芳基溴化物、芳基碘化物和三氟甲磺酸，以及反应性相对较低的芳基氯化物。在氨基羰基化条件下，可以容忍底物芳环上的各种官能团。催化氨基羰基化反应制备了驱虫剂N , N-二乙基-3-甲基苯甲酰胺以及二氢叶酸还原酶抑制剂三嗪酸盐的合成中间体。
• Kinase Scaffold Repurposing for Neglected Disease Drug Discovery: Discovery of an Efficacious, Lapatanib-Derived Lead Compound for Trypanosomiasis
  作者：Gautam Patel、Caitlin E. Karver、Ranjan Behera、Paul J. Guyett、Catherine Sullenberger、Peter Edwards、Norma E. Roncal、Kojo Mensa-Wilmot、Michael P. Pollastri

  DOI：10.1021/jm400349k

  日期：2013.5.23

  Human African trypanosomiasis (HAT) is a neglected tropical disease caused by the protozoan parasite Trypanosoma brucei. Because drugs in use against HAT are toxic and require intravenous dosing, new drugs are needed. Initiating lead discovery campaigns by using chemical scaffolds from drugs approved for other indications can speed up drug discovery for neglected diseases. We demonstrated recently that the 4-anilinoquinazolines lapatinib (GW572016, 1) and canertinib (CI-1033) kill T. brucei with low micromolar EC50 values. We now report promising activity of analogues of 1, which provided an excellent starting point for optimization of the chemotype. Our compound optimization that has led to synthesis of several potent 4-anilinoquinazolines, including NEU617, 23a, a highly potent, orally bioavailable inhibitor of trypanosome replication. At the cellular level, 23a blocks duplication of the kinetoplast and arrests cytokinesis, making it a new chemical tool for studying regulation of the trypanosome cell cycle.