methyl 2-(3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)acetate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl 2-(3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)acetate
• 英文别名: methyl [3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetate；methyl 2-[3-(trifluoromethyl)-4,5,6,7-tetrahydroindazol-1-yl]acetate
• 化学式: C₁₁H₁₃F₃N₂O₂
• mdl: MFCD02732815
• 分子量: 262.232
• InChiKey: XEWXUSDUHJVSBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2-(3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)acetate 在 叠氮基三甲基硅烷 、 copper diacetate 、 2,2′-双[(4S)-4-苄基-2-噁唑啉] 、 N-氟代双苯磺酰胺 作用下， 以 硝基甲烷 为溶剂， 反应 24.0h， 以65%的产率得到methyl 2-(4-azido-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)acetate
  参考文献：
  名称：

  Site-Selective Copper-Catalyzed Azidation of Benzylic C–H Bonds

  摘要：

  Site selectivity represents a key challenge for non-directed C-H functionalization, even when the C-H bond is intrinsically reactive. Here, we report a copper-catalyzed method for benzylic C-H azidation of diverse molecules. Experimental and density functional theory studies suggest the benzyl radical reacts with a Cu-II-azide species via a radical-polar crossover pathway. Comparison of this method with other C-H azidation methods highlights its unique site selectivity, and conversions of the benzyl azide products into amine, triazole, tetrazole, and pyrrole functional groups highlight the broad utility of this method for target molecule synthesis and medicinal chemistry.

  DOI：

  10.1021/jacs.0c05362

文献信息

• Benzylic C–H isocyanation/amine coupling sequence enabling high-throughput synthesis of pharmaceutically relevant ureas
  作者：Sung-Eun Suh、Leah E. Nkulu、Shishi Lin、Shane W. Krska、Shannon S. Stahl

  DOI：10.1039/d1sc02049h

  日期：——

  selectivity and good functional group tolerance, and uses commercially available catalyst components and reagents [CuOAc, 2,2′-bis(oxazoline) ligand, (trimethylsilyl)isocyanate, and N-fluorobenzenesulfonimide]. The isocyanate products may be used without isolation or purification in a subsequent coupling step with primary and secondary amines to afford hundreds of diverse ureas. These results provide

  C(sp 3 )–H 功能化方法为药物化学提供了理想的合成平台；然而，这些方法通常受到实际限制的限制。本研究概述了一种 C(sp 3 )–H 异氰化方案，该方案能够以高通量形式合成多种药学相关的苄基脲。操作简单的 C-H 异氰化方法显示出高位点选择性和良好的官能团耐受性，并使用市售的催化剂组分和试剂 [CuOAc、2,2'-双（恶唑啉）配体、（三甲基甲硅烷基）异氰酸酯和N-氟苯磺酰亚胺]。异氰酸酯产物无需分离或纯化即可用于后续与伯胺和仲胺的偶联步骤，以提供数百种不同的脲。这些结果为在药物发现中实施 C-H 功能化/交叉偶联提供了模板。
• Site-Selective Copper-Catalyzed Azidation of Benzylic C–H Bonds
  作者：Sung-Eun Suh、Si-Jie Chen、Mukunda Mandal、Ilia A. Guzei、Christopher J. Cramer、Shannon S. Stahl

  DOI：10.1021/jacs.0c05362

  日期：2020.7.1

  Site selectivity represents a key challenge for non-directed C-H functionalization, even when the C-H bond is intrinsically reactive. Here, we report a copper-catalyzed method for benzylic C-H azidation of diverse molecules. Experimental and density functional theory studies suggest the benzyl radical reacts with a Cu-II-azide species via a radical-polar crossover pathway. Comparison of this method with other C-H azidation methods highlights its unique site selectivity, and conversions of the benzyl azide products into amine, triazole, tetrazole, and pyrrole functional groups highlight the broad utility of this method for target molecule synthesis and medicinal chemistry.