4-(6-bromopyridin-3-yloxy)-7-methoxyquinoline | 1039046-54-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(6-bromopyridin-3-yloxy)-7-methoxyquinoline
• 英文别名: 4-((6-Bromopyridin-3-yl)oxy)-7-methoxyquinoline；4-(6-bromopyridin-3-yl)oxy-7-methoxyquinoline
• CAS: 1039046-54-2
• 化学式: C₁₅H₁₁BrN₂O₂
• 分子量: 331.169
• InChiKey: GQYBZLQCLWYCLS-UHFFFAOYSA-N

物化性质

• 沸点：
  468.6±40.0 °C(Predicted)
• 密度：
  1.500±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-(6-bromopyridin-3-yloxy)-7-methoxyquinoline 在 tris-(dibenzylideneacetone)dipalladium(0) 、 lithium hexamethyldisilazane 、 2-(二环己基膦基)联苯 作用下， 以 1,3-二噁烷 为溶剂， 反应 21.0h， 以73%的产率得到5-(7-methoxyquinolin-4-yloxy)pyridin-2-amine
  参考文献：
  名称：

  Discovery of a Potent, Selective, and Orally Bioavailable c-Met Inhibitor: 1-(2-Hydroxy-2-methylpropyl)-N-(5-(7-methoxyquinolin-4-yloxy)pyridin-2-yl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (AMG 458)

  摘要：

  Deregulation of the receptor tyrosine kinase c-Met has been implicated in human cancers. Pyrazolones with N-1 bearing a pendent hydroxyalkyl side chain showed selective inhibition of c-Met over VEGFR2. However, studies revealed the generation of active, nonselective metabolites. Blocking this metabolic hot spot led to the discovery of 17 (AMG 458). When dosed orally, 17 significantly inhibited tumor growth in the NIH3T3/FPR-Met and U-87 MG xenograft models with no adverse effect on body weight.

  DOI：

  10.1021/jm800401t
• 作为产物：
  描述：

  2-溴-5-羟基吡啶 、 4-氯-7-甲氧基喹啉 以 氯苯 为溶剂， 反应 24.0h， 以97%的产率得到4-(6-bromopyridin-3-yloxy)-7-methoxyquinoline
  参考文献：
  名称：

  Discovery of a Potent, Selective, and Orally Bioavailable c-Met Inhibitor: 1-(2-Hydroxy-2-methylpropyl)-N-(5-(7-methoxyquinolin-4-yloxy)pyridin-2-yl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (AMG 458)

  摘要：

  Deregulation of the receptor tyrosine kinase c-Met has been implicated in human cancers. Pyrazolones with N-1 bearing a pendent hydroxyalkyl side chain showed selective inhibition of c-Met over VEGFR2. However, studies revealed the generation of active, nonselective metabolites. Blocking this metabolic hot spot led to the discovery of 17 (AMG 458). When dosed orally, 17 significantly inhibited tumor growth in the NIH3T3/FPR-Met and U-87 MG xenograft models with no adverse effect on body weight.

  DOI：

  10.1021/jm800401t

文献信息

• <i>ortho</i>-Selective Dearomative [2π + 2σ] Photocycloadditions of Bicyclic Aza-Arenes
  作者：Roman Kleinmans、Subhabrata Dutta、Kristers Ozols、Huiling Shao、Felix Schäfer、Rebecca E. Thielemann、Hok Tsun Chan、Constantin G. Daniliuc、Kendall N. Houk、Frank Glorius

  DOI：10.1021/jacs.3c02961

  日期：2023.6.7

  Dearomative photocycloadditions are valuable chemical transformations, serving as an efficient platform to create three-dimensional molecular complexity. However, the photolability of the original addition product especially within the context of ortho cycloadditions often causes undesired consecutive rearrangements, rendering these ortho cycloadducts elusive. Herein, we report an ortho-selective intermolecular

  脱芳烃光环加成是有价值的化学转化，可作为创建三维分子复杂性的有效平台。然而，原始加成产物的光不稳定性，尤其是在邻位环加成的情况下，通常会导致不需要的连续重排，从而使这些邻位环加合物难以捉摸。在此，我们通过利用应变释放方法报告了双环氮杂芳烃（包括（异）喹啉、喹唑啉和喹喔啉）的邻位选择性分子间光环加成。以双环 [1.1.0] 丁烷作为偶联伙伴，这种去芳香化 [2π + 2σ] 环加成可以直接构建 C(sp 3)-富含二环[2.1.1]己烷直接连接到N-杂芳烃。光物理实验和 DFT 计算揭示了 [2π + 2σ] 选择性的起源，并表明，除了最初提出的能量转移或直接激发途径外，链式反应机制根据反应条件起作用。
• Discovery of a Potent, Selective, and Orally Bioavailable c-Met Inhibitor: 1-(2-Hydroxy-2-methylpropyl)-<i>N</i>-(5-(7-methoxyquinolin-4-yloxy)pyridin-2-yl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1<i>H</i>-pyrazole-4-carboxamide (AMG 458)
  作者：Longbin Liu、Aaron Siegmund、Ning Xi、Paula Kaplan-Lefko、Karen Rex、April Chen、Jasmine Lin、Jodi Moriguchi、Loren Berry、Liyue Huang、Yohannes Teffera、Yajing Yang、Yihong Zhang、Steven F. Bellon、Matthew Lee、Roman Shimanovich、Annette Bak、Celia Dominguez、Mark H. Norman、Jean-Christophe Harmange、Isabelle Dussault、Tae-Seong Kim

  DOI：10.1021/jm800401t

  日期：2008.7

  Deregulation of the receptor tyrosine kinase c-Met has been implicated in human cancers. Pyrazolones with N-1 bearing a pendent hydroxyalkyl side chain showed selective inhibition of c-Met over VEGFR2. However, studies revealed the generation of active, nonselective metabolites. Blocking this metabolic hot spot led to the discovery of 17 (AMG 458). When dosed orally, 17 significantly inhibited tumor growth in the NIH3T3/FPR-Met and U-87 MG xenograft models with no adverse effect on body weight.