trans-ethyl 2-(2-(trifluoromethyl)phenyl)cyclopropanecarboxylate

• 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: trans-ethyl 2-(2-(trifluoromethyl)phenyl)cyclopropanecarboxylate
• 英文别名: Ethyl trans-2-[2-(Trifluoromethyl)phenyl]cyclopropanecarboxylate；ethyl (1R,2R)-2-[2-(trifluoromethyl)phenyl]cyclopropane-1-carboxylate
• 化学式: C₁₃H₁₃F₃O₂
• 分子量: 258.24
• InChiKey: VCBBPVCZTUXWNA-VHSXEESVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  trans-ethyl 2-(2-(trifluoromethyl)phenyl)cyclopropanecarboxylate 在 甲醇 、 potassium hydroxide 作用下， 生成 (1R*,2R*)-2-<2-(trifluoromethyl)phenyl>cyclopropanecarboxylic acid
  参考文献：
  名称：

  Selective 5-Hydroxytryptamine 2C Receptor Agonists Derived from the Lead Compound Tranylcypromine: Identification of Drugs with Antidepressant-Like Action

  摘要：

  We report here the design, synthesis, and pharmacological properties of a series of compounds related to tranylcypromine (9), which itself was discovered as a lead compound in a high-throughput screening campaign. Starting from 9, which shows modest activity as a 5-HT2C agonist, a series of 1-aminomethyl-2-phenylcyclopropanes was investigated as 5-HT2C agonists through iterative structural modifications. Key pharmacophore feature of this new class of ligands is a 2-aminomethyl-trans-cyclopropyl side chain attached to a substituted benzene ring. Among the tested compounds, several were potent and efficacious 5-HT2C receptor agonists with selectivity over both 5-HT2A and 5-HT2B receptors in functional assays. The most promising compound is 37, with 120- and 14-fold selectivity over 5-HT2A and 5-HT2B, respectively (EC50 = 585, 65, and 4.8 nM at the 2A, 2B, and 2C subtypes, respectively). In animal studies, compound 37 (10-60 mg/kg) decreased immobility time in the mouse forced swim test.

  DOI：

  10.1021/jm801354e
• 作为产物：
  描述：

  邻溴三氟甲苯 、 potassium (trans-2-(ethoxycarbonyl)cyclopropyl)trifluoroborate 在 palladium diacetate 、 caesium carbonate 、 正丁基二(1-金刚烷基)膦 作用下， 以 水 、 甲苯 为溶剂， 反应 12.0h， 以50%的产率得到trans-ethyl 2-(2-(trifluoromethyl)phenyl)cyclopropanecarboxylate
  参考文献：
  名称：

  功能化的1,2-二取代环丙基三氟硼酸酯的多谱图合成和C-C / C-N偶联

  摘要：

  基于Pd（II）或Cu（I）催化的三氟硼酸乙烯基酯与重氮化合物的反应，开发了一种方便的方法，用于功能化的1,2-二取代的环丙基三氟硼酸酯的多谱合成。优化的方案允许将目标产物制备为数克级的纯非对映异构体。结果表明，标题化合物是Suzuki-Miyaura和Chan-Lam反应的良好偶联伙伴，可提供与医学相关的（杂）芳基环丙烷，具有高非对映选择性。

  DOI：

  10.1002/adsc.201900879

文献信息

• Multigram Synthesis and C−C/C−N Couplings of Functionalized 1,2‐Disubstituted Cyclopropyltrifluoroborates
  作者：Oleksandr V. Hryschuk、Yevhen Yurov、Andriy V. Tymtsunik、Volodymyr O. Kovtunenko、Igor V. Komarov、Oleksandr O. Grygorenko

  DOI：10.1002/adsc.201900879

  日期：2019.12.3

  A convenient approach to the multigram synthesis of functionalized 1,2‐disubstituted cyclopropyltrifluoroborates was developed, based on Pd(II)‐ or Cu(I)‐catalyzed reaction of vinyltrifluoroborate and diazo compounds. Optimized protocols allowed for the preparation of the target products as pure diastereomers on multigram scale. It was shown that the title compounds were good coupling partners for

  基于Pd（II）或Cu（I）催化的三氟硼酸乙烯基酯与重氮化合物的反应，开发了一种方便的方法，用于功能化的1,2-二取代的环丙基三氟硼酸酯的多谱合成。优化的方案允许将目标产物制备为数克级的纯非对映异构体。结果表明，标题化合物是Suzuki-Miyaura和Chan-Lam反应的良好偶联伙伴，可提供与医学相关的（杂）芳基环丙烷，具有高非对映选择性。
• Selective 5-Hydroxytryptamine 2C Receptor Agonists Derived from the Lead Compound Tranylcypromine: Identification of Drugs with Antidepressant-Like Action
  作者：Sung Jin Cho、Niels H. Jensen、Toru Kurome、Sudhakar Kadari、Michael L. Manzano、Jessica E. Malberg、Barbara Caldarone、Bryan L. Roth、Alan P. Kozikowski

  DOI：10.1021/jm801354e

  日期：2009.4.9

  We report here the design, synthesis, and pharmacological properties of a series of compounds related to tranylcypromine (9), which itself was discovered as a lead compound in a high-throughput screening campaign. Starting from 9, which shows modest activity as a 5-HT2C agonist, a series of 1-aminomethyl-2-phenylcyclopropanes was investigated as 5-HT2C agonists through iterative structural modifications. Key pharmacophore feature of this new class of ligands is a 2-aminomethyl-trans-cyclopropyl side chain attached to a substituted benzene ring. Among the tested compounds, several were potent and efficacious 5-HT2C receptor agonists with selectivity over both 5-HT2A and 5-HT2B receptors in functional assays. The most promising compound is 37, with 120- and 14-fold selectivity over 5-HT2A and 5-HT2B, respectively (EC50 = 585, 65, and 4.8 nM at the 2A, 2B, and 2C subtypes, respectively). In animal studies, compound 37 (10-60 mg/kg) decreased immobility time in the mouse forced swim test.