3-bromo-4-(3,4,5-trimethoxyphenyl)thiophene | 1312996-56-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-bromo-4-(3,4,5-trimethoxyphenyl)thiophene
• CAS: 1312996-56-7
• 化学式: C₁₃H₁₃BrO₃S
• 分子量: 329.214
• InChiKey: PTJIGDAQBJMXTI-UHFFFAOYSA-N

物化性质

• 熔点：
  90.7-91.2 °C
• 沸点：
  346.9±42.0 °C(Predicted)
• 密度：
  1.416±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  55.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-bromo-4-(3,4,5-trimethoxyphenyl)thiophene 、 2,3-二甲氧基苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate decahydrate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 以74%的产率得到3-(2,3-dimethoxyphenyl)-4-(3,4,5-trimethoxyphenyl)thiophene
  参考文献：
  名称：

  Regioselective Suzuki Coupling of Dihaloheteroaromatic Compounds as a Rapid Strategy To Synthesize Potent Rigid Combretastatin Analogues

  摘要：

  Combretastatin A-4 (CA-4) is a potent tubulin depolymerizing agent able to inhibit tumor growth and with antivascular effects. Although it is in clinical trials, the search for novel analogues that may display better/different features is still ongoing. In this manuscript we describe the synthesis of novel constrained analogues of CA-4 obtained in only two synthetic steps exploiting a regioselective Suzuki coupling of dihalogenated heteroaromatic and alicyclic compounds. All the compounds synthesized have been evaluated for cytotoxicity and for their ability to inhibit tubulin assembly. One of them, 38, displayed low nanomolar cytotoxicity and proved to have a pharmacodynamic profile similar to that of CA-4 and a better pharmacokinetic profile, but most important of all, this synthetic strategy may pave the way for the easy and rapid generation of novel rigid analogues of combretastatins.

  DOI：

  10.1021/jm200555r
• 作为产物：
  描述：

  3,4-二溴噻吩 、 3,4,5-三甲氧基苯硼酸 在 palladium diacetate 、 cesium fluoride 、 1,5-环辛二烯 、 2-二-叔丁膦基-2',4',6'-三异丙基联苯 作用下， 以 水 为溶剂， 反应 1.65h， 以14%的产率得到3-bromo-4-(3,4,5-trimethoxyphenyl)thiophene
  参考文献：
  名称：

  通过原位结晶选择性机械化学单芳基化无偏二溴芳烃

  摘要：

  在机械化学条件下，钯催化的液体无偏二溴芳烃的 Suzuki-Miyaura 交叉偶联反应选择性地提供单芳基化产物。结晶单芳基化产物相对于液体原料的较低反应性主要归因于前者在反应混合物中的低扩散效率，这导致选择性单芳基化。本研究揭示了一种新方法，该方法使用固体中的原位相变来设计通过传统的基于溶液的合成难以实现的选择性有机转化。

  DOI：

  10.1021/jacs.0c01739

文献信息

• Selective Mechanochemical Monoarylation of Unbiased Dibromoarenes by <i>in Situ</i> Crystallization
  作者：Tamae Seo、Koji Kubota、Hajime Ito

  DOI：10.1021/jacs.0c01739

  日期：2020.6.3

  Palladium-catalyzed Suzuki-Miyaura cross-coupling reactions of liquid, unbiased dibromoarenes under mechanochemical conditions selectively afford the monoarylated products. The lower reactivity of the crystalline monoarylated products rela-tive to the liquid starting materials should be attributed predom-inantly to the low diffusion efficiency of the former in the re-action mixture, which results in

  在机械化学条件下，钯催化的液体无偏二溴芳烃的 Suzuki-Miyaura 交叉偶联反应选择性地提供单芳基化产物。结晶单芳基化产物相对于液体原料的较低反应性主要归因于前者在反应混合物中的低扩散效率，这导致选择性单芳基化。本研究揭示了一种新方法，该方法使用固体中的原位相变来设计通过传统的基于溶液的合成难以实现的选择性有机转化。
• Regioselective Suzuki Coupling of Dihaloheteroaromatic Compounds as a Rapid Strategy To Synthesize Potent Rigid Combretastatin Analogues
  作者：Sewan Theeramunkong、Antonio Caldarelli、Alberto Massarotti、Silvio Aprile、Diego Caprioglio、Roberta Zaninetti、Alessia Teruggi、Tracey Pirali、Giorgio Grosa、Gian Cesare Tron、Armando A. Genazzani

  DOI：10.1021/jm200555r

  日期：2011.7.28

  Combretastatin A-4 (CA-4) is a potent tubulin depolymerizing agent able to inhibit tumor growth and with antivascular effects. Although it is in clinical trials, the search for novel analogues that may display better/different features is still ongoing. In this manuscript we describe the synthesis of novel constrained analogues of CA-4 obtained in only two synthetic steps exploiting a regioselective Suzuki coupling of dihalogenated heteroaromatic and alicyclic compounds. All the compounds synthesized have been evaluated for cytotoxicity and for their ability to inhibit tubulin assembly. One of them, 38, displayed low nanomolar cytotoxicity and proved to have a pharmacodynamic profile similar to that of CA-4 and a better pharmacokinetic profile, but most important of all, this synthetic strategy may pave the way for the easy and rapid generation of novel rigid analogues of combretastatins.