2-chloro-5-fluoro-4-(4-fluorophenyl)pyrimidine | 1341200-71-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-chloro-5-fluoro-4-(4-fluorophenyl)pyrimidine
• 英文别名: 2-Chloro-5-fluoro-4-(4-fluorophenyl)pyrimidine
• CAS: 1341200-71-2
• 化学式: C₁₀H₅ClF₂N₂
• 分子量: 226.613
• InChiKey: ZHYRICQPUPMTEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-5-fluoro-4-(4-fluorophenyl)pyrimidine 在 氯磺酸 作用下， 反应 4.0h， 以72%的产率得到2-(2-chloro-5-fluoropyrimidin-4-yl)-5-fluorobenzene-1-sulfonyl chloride
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of a Series of Novel AXL Kinase Inhibitors

  摘要：

  The receptor tyrosine kinase AXL has emerged in recent years as an potential oncology target due to its overexpression in several types of cancers coupled with its ability to promote tumor growth and metastasis. To identify small molecule inhibitors of AXL, we built a homology model of its catalytic domain to virtually screen and identify scaffolds displaying an affinity for AXL. Further computational and structure-based design resulted in the synthesis of a series of 2,4,5-trisubstitued pyrimidines, which demonstrated potent inhibition of AXL in vitro (IC(50) = 19 nM) and strongly inhibited the growth of several pancreatic cell lines.

  DOI：

  10.1021/ml200198x
• 作为产物：
  描述：

  4-氟苯硼酸 、 2,4-二氯-5-氟嘧啶 在 palladium diacetate 、 sodium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 12.0h， 以100%的产率得到2-chloro-5-fluoro-4-(4-fluorophenyl)pyrimidine
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of a Series of Novel AXL Kinase Inhibitors

  摘要：

  The receptor tyrosine kinase AXL has emerged in recent years as an potential oncology target due to its overexpression in several types of cancers coupled with its ability to promote tumor growth and metastasis. To identify small molecule inhibitors of AXL, we built a homology model of its catalytic domain to virtually screen and identify scaffolds displaying an affinity for AXL. Further computational and structure-based design resulted in the synthesis of a series of 2,4,5-trisubstitued pyrimidines, which demonstrated potent inhibition of AXL in vitro (IC(50) = 19 nM) and strongly inhibited the growth of several pancreatic cell lines.

  DOI：

  10.1021/ml200198x

文献信息

• Intramolecular Inverse Electron-Demand [4 + 2] Cycloadditions of Ynamides with Pyrimidines: Scope and Density Functional Theory Insights
  作者：Guillaume Duret、Robert Quinlan、Boyang Yin、Rainer E. Martin、Philippe Bisseret、Markus Neuburger、Vincent Gandon、Nicolas Blanchard

  DOI：10.1021/acs.joc.6b02986

  日期：2017.2.3

  prepared in only three steps from commercially available pyrimidines. The key step of this short sequence is a [4 + 2]/retro-[4 + 2] cycloaddition between a pyrimidine and an ynamide, which constitutes the first examples of ynamides behaving as electron-rich dienophiles in [4 + 2] cycloaddition reactions. In addition, running the ihDA/rDA reaction in continuous mode in superheated toluene, to overcome

  从生命科学到催化，4-氨基吡啶通常是化学工业中有价值的支架。我们在这里报告了结构多样的多环稠合和螺-4-氨基吡啶的集合，它们仅需三步即可从市售嘧啶中制备。此短序列的关键步骤是嘧啶和乙酰胺之间的[4 + 2] /复古-[4 + 2]环加成，这构成了乙酰胺中的首个实例，在[4 + 2]环加成中表现为富电子的亲二烯体。反应。此外，与间歇模式相比，在过热的甲苯中以连续模式运行ihDA / rDA反应可克服MW反应有限的可扩展性，从而显着提高产量。最后，
• Inverse Electron-Demand [4 + 2]-Cycloadditions of Ynamides: Access to Novel Pyridine Scaffolds
  作者：Guillaume Duret、Robert Quinlan、Rainer E. Martin、Philippe Bisseret、Markus Neuburger、Vincent Gandon、Nicolas Blanchard

  DOI：10.1021/acs.orglett.6b00464

  日期：2016.4.1

  still hampered by a number of shortcomings. These nitrogenated heterocycles can be efficiently prepared by an intramolecular inverse electron demand hetero Diels–Alder (ihDA) cycloaddition of ynamides to pyrimidines. This ihDA/rDA sequence is general in scope and affords expedient access to novel types of aminopyridinyl scaffolds that hold great promise in terms of exit vector patterns.

  功能化的多环氨基吡啶是化学科学的中心，但是它们的合成仍然受到许多缺点的阻碍。这些氮化的杂环可以通过酰胺内酰胺与嘧啶的分子内逆电子需求异狄尔斯-阿尔德（ih DA）环加成反应而有效地制备。该ihDA / rDA序列的范围很广，可以方便地获得新型的氨基吡啶基支架，就出口载体模式而言，它们具有广阔的前景。
• Design, Synthesis, and Biological Evaluation of a Series of Novel AXL Kinase Inhibitors
  作者：Alexis Mollard、Steven L. Warner、Lee T. Call、Mark L. Wade、Jared J. Bearss、Anupam Verma、Sunil Sharma、Hariprasad Vankayalapati、David J. Bearss

  DOI：10.1021/ml200198x

  日期：2011.12.8

  The receptor tyrosine kinase AXL has emerged in recent years as an potential oncology target due to its overexpression in several types of cancers coupled with its ability to promote tumor growth and metastasis. To identify small molecule inhibitors of AXL, we built a homology model of its catalytic domain to virtually screen and identify scaffolds displaying an affinity for AXL. Further computational and structure-based design resulted in the synthesis of a series of 2,4,5-trisubstitued pyrimidines, which demonstrated potent inhibition of AXL in vitro (IC(50) = 19 nM) and strongly inhibited the growth of several pancreatic cell lines.