5-methoxy-2-(4-methoxyphenyl)-3-(trifluoromethyl)-2H-indazole | 848142-75-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-methoxy-2-(4-methoxyphenyl)-3-(trifluoromethyl)-2H-indazole
• 英文别名: Vbchem314_0m_a；5-methoxy-2-(4-methoxyphenyl)-3-(trifluoromethyl)indazole
• CAS: 848142-75-6
• 化学式: C₁₆H₁₃F₃N₂O₂
• 分子量: 322.287
• InChiKey: RMPGIJZHOCSLDY-UHFFFAOYSA-N

物化性质

• 熔点：
  128-129 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  309.1±42.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  36.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-methoxy-2-(4-methoxyphenyl)-3-(trifluoromethyl)-2H-indazole 在 三氟二甲基硫醚络合物 作用下， 以 二氯甲烷 为溶剂， 生成 2-(4-Hydroxyphenyl)-3-(trifluoromethyl)indazol-5-ol
  参考文献：
  名称：

  在离子液体中使用 TT-CF3+OTf− 光氧化还原催化 2H-吲唑的三氟甲基化

  摘要：

  通过使用曙红 Y 作为光催化剂和可回收离子液体作为溶剂，开发了一种无金属和氧化剂的光氧化还原催化 2 H-吲唑三氟甲基化的方案。在该协议中，在温和条件下，以中等到良好的收率获得了一系列三氟甲基化产品。该反应通过自由基机制进行，具有广泛的底物范围、优异的区域选择性和良好的官能团耐受性。此外，该协议的实用性通过雌激素受体β（ERβ）和药物格拉司琼的高选择性配体的合成得到证明。该协议为三氟甲基化反应提供了一种温和且环保的解决方案。

  DOI：

  10.1039/d3ob00096f
• 作为产物：
  描述：

  4-甲氧基苯肼盐酸盐 在 1,1'-双(二苯基膦)二茂铁 、 palladium diacetate 、 copper(l) iodide 、 溴 、 sodium hexamethyldisilazane 、 溶剂黄146 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 31.25h， 生成 5-methoxy-2-(4-methoxyphenyl)-3-(trifluoromethyl)-2H-indazole
  参考文献：
  名称：

  Indazole Estrogens:  Highly Selective Ligands for the Estrogen Receptor β

  摘要：

  The estrogen receptors, ERalpha and ERbeta, are important pharmaceutical targets. To develop ERbeta-selective ligands, we synthesized a series of nonsteroidal compounds having a phenyl-2H-indazole core with different groups at C-3. Several of these show high affinity and good ERbeta selectivity, especially those with polar and/or polarizable substituents at this site (halogen, CF3, nitrile); the best compounds have affinities for ERbeta comparable to estradiol, with ERbeta affinity selectivity > 100. This potency and ERbeta selectivity is also seen in cell-based transcriptional assays, where several compounds showed ERbeta efficacies equivalent to that of estradiol with ERbeta potency selectivities of 100. These compounds might prove useful as selective pharmacological probes to study the biological actions of estrogens mediated through ERP, and they might lead to the development of useful pharmaceuticals. These findings also contribute to an evolving pharmacophore that characterizes certain nonsteroidal ligands having high ERbeta subtype affinity and potency selectivity.

  DOI：

  10.1021/jm049223g

文献信息

• Electrochemically mediated trifluoromethylation of 2H-indazole derivatives using CF3SO2Na
  作者：Tingting Wei、Kai Wang、Zhichen Yu、Jiahao Hou、Yuanyuan Xie

  DOI：10.1016/j.tetlet.2021.153313

  日期：2021.12

  An environmentally friendly method of electrochemical mediated regioselective C-3 trifluoromethylation of 2H-indazole by employing CF3SO2Na as the CF3 source was described. This reaction tolerated various functional groups and provided CH trifluoromethylated products in moderate to good yields under transition metal-free and oxidant-free reaction conditions. Mechanism experiments showed that a radical

  描述了一种以 CF 3 SO 2 Na 作为 CF 3源的电化学介导的 2H-吲唑区域选择性 C-3 三氟甲基化的环境友好方法。该反应耐受各种官能团，并在无过渡金属和无氧化剂的反应条件下以中等至良好的产率提供 C H 三氟甲基化产物。机理实验表明，这种转变可能涉及一个激进的过程。
• Metal-Free Trifluoromethylation of Indazoles
  作者：Payel Ghosh、Susmita Mondal、Alakananda Hajra

  DOI：10.1021/acs.joc.8b02312

  日期：2018.11.2

  A simple and efficient tert-butyl hydroperoxide-mediated direct trifluoromethylation of indazoles using sodium trifluoromethanesulfinate has been developed under metal-free conditions. A library of trifluoromethylated products with broad functionalities has been synthesized with moderate to good yields. A radical mechanistic pathway has been proposed for the present protocol.

  在无金属的条件下，开发了一种简单有效的氢过氧化物叔丁基介导的吲唑直接三氟甲基化反应，该反应使用三氟甲亚磺酸钠。合成了具有广泛功能的三氟甲基化产物库，产率中等至良好。已经为本方案提出了一种根本性的机械途径。
• Indazole Estrogens:  Highly Selective Ligands for the Estrogen Receptor β
  作者：Meri De Angelis、Fabio Stossi、Kathryn A. Carlson、Benita S. Katzenellenbogen、John A. Katzenellenbogen

  DOI：10.1021/jm049223g

  日期：2005.2.1

  The estrogen receptors, ERalpha and ERbeta, are important pharmaceutical targets. To develop ERbeta-selective ligands, we synthesized a series of nonsteroidal compounds having a phenyl-2H-indazole core with different groups at C-3. Several of these show high affinity and good ERbeta selectivity, especially those with polar and/or polarizable substituents at this site (halogen, CF3, nitrile); the best compounds have affinities for ERbeta comparable to estradiol, with ERbeta affinity selectivity > 100. This potency and ERbeta selectivity is also seen in cell-based transcriptional assays, where several compounds showed ERbeta efficacies equivalent to that of estradiol with ERbeta potency selectivities of 100. These compounds might prove useful as selective pharmacological probes to study the biological actions of estrogens mediated through ERP, and they might lead to the development of useful pharmaceuticals. These findings also contribute to an evolving pharmacophore that characterizes certain nonsteroidal ligands having high ERbeta subtype affinity and potency selectivity.
• Photoredox-catalyzed trifluoromethylation of 2<i>H</i>-indazoles using TT-CF₃⁺OTf⁻ in ionic liquids
  作者：Xin He、Zhicheng Chen、Xianghui Zhu、Hao Liu、Yanjie Chen、Zhizhong Sun、Wenyi Chu

  DOI：10.1039/d3ob00096f

  日期：——

  A protocol for metal and oxidant free photoredox catalyzed trifluoromethylation of 2H-indazoles was developed by using Eosin Y as the photocatalyst and recoverable ionic liquids as the solvents. A series of trifluoromethylated products were obtained in moderate to good yields in this protocol under mild conditions. The reaction proceeded via a free-radical mechanism with a broad substrate range, excellent

  通过使用曙红 Y 作为光催化剂和可回收离子液体作为溶剂，开发了一种无金属和氧化剂的光氧化还原催化 2 H-吲唑三氟甲基化的方案。在该协议中，在温和条件下，以中等到良好的收率获得了一系列三氟甲基化产品。该反应通过自由基机制进行，具有广泛的底物范围、优异的区域选择性和良好的官能团耐受性。此外，该协议的实用性通过雌激素受体β（ERβ）和药物格拉司琼的高选择性配体的合成得到证明。该协议为三氟甲基化反应提供了一种温和且环保的解决方案。