8-(fluoromethyl)-1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione | 501005-27-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 8-(fluoromethyl)-1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione
• 英文别名: 8-(Fluoromethyl)-1,3,7-trimethylpurine-2,6-dione
• CAS: 501005-27-2
• 化学式: C₉H₁₁FN₄O₂
• 分子量: 226.21
• InChiKey: AXXQFBYOHQLECI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  58.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  咖啡因 、 2-((ethoxycarbonothioyl)thio)-2-fluoroacetic acid 在 过氧化双月桂酰 作用下， 以 乙酸乙酯 为溶剂， 反应 9.0h， 以29%的产率得到8-(fluoromethyl)-1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione
  参考文献：
  名称：

  便宜的杂芳烃的自由基甲基化和相关的烷基化

  摘要：

  描述了一种使用非常便宜的试剂将甲基和高级脂肪族基团引入各种杂芳烃的简单方法。它基于羧酸黄原酸酯的自由基加成，然后进行脱羧。取决于杂芳烃结构，脱羧可以是自发的，或者可以通过在微波炉中的N，N-二甲基乙酰胺或N-甲基吡咯烷酮中加热来引发。

  DOI：

  10.1021/acs.orglett.8b00190

文献信息

• Practical and innate carbon–hydrogen functionalization of heterocycles
  作者：Yuta Fujiwara、Janice A. Dixon、Fionn O’Hara、Erik Daa Funder、Darryl D. Dixon、Rodrigo A. Rodriguez、Ryan D. Baxter、Bart Herlé、Neal Sach、Michael R. Collins、Yoshihiro Ishihara、Phil S. Baran

  DOI：10.1038/nature11680

  日期：2012.12.6

  It is shown that zinc sulphinate salts can be used to transfer alkyl radicals to heterocycles, allowing for the mild, direct and operationally simple formation of medicinally relevant carbon–carbon bonds while reacting in a complementary fashion to other innate carbon–hydrogen functionalization methods. Nitrogen-rich heterocycles feature widely in pharmaceuticals, and their synthesis has been simplified by a series of advances in transition-metal-mediated cross-coupling reactions. However, the development of practical and selective C–H functionalization methods that do not rely upon pre-functionalized starting materials is an underdeveloped area. Here the authors report that zinc sulphinate salts can be used to transfer alkyl radicals to heterocycles, allowing for a mild, direct and operationally simple formation of medicinally relevant C–C bonds while reacting in an orthogonal fashion to other innate C–H functionalization methods. Nitrogen-rich heterocyclic compounds have had a profound effect on human health because these chemical motifs are found in a large number of drugs used to combat a broad range of diseases and pathophysiological conditions. Advances in transition-metal-mediated cross-coupling have simplified the synthesis of such molecules; however, C–H functionalization of medicinally important heterocycles that does not rely on pre-functionalized starting materials is an underdeveloped area1,2,3,4,5,6,7,8,9. Unfortunately, the innate properties of heterocycles that make them so desirable for biological applications—such as aqueous solubility and their ability to act as ligands—render them challenging substrates for direct chemical functionalization. Here we report that zinc sulphinate salts can be used to transfer alkyl radicals to heterocycles, allowing for the mild (moderate temperature, 50 °C or less), direct and operationally simple formation of medicinally relevant C–C bonds while reacting in a complementary fashion to other innate C–H functionalization methods2,3,4,5,6 (Minisci, borono-Minisci, electrophilic aromatic substitution, transition-metal-mediated C–H insertion and C–H deprotonation). We prepared a toolkit of these reagents and studied their reactivity across a wide range of heterocycles (natural products, drugs and building blocks) without recourse to protecting-group chemistry. The reagents can even be used in tandem fashion in a single pot in the presence of water and air.

  研究表明，亚磺酸锌盐可用于将烷基自由基转移到杂环上，从而在与其他固有的碳氢官能化方法互补反应的同时，温和、直接且操作简便地形成具有药物相关性的碳-碳键。含氮杂环在药物中广泛存在，过渡金属介导的交叉偶联反应的一系列进展简化了它们的合成。然而，不依赖预官能化起始材料的实用且选择性的碳氢官能化方法是一个发展不足的领域。在这里，作者报道亚磺酸锌盐可用于将烷基自由基转移到杂环上，从而在与其他固有的碳氢官能化方法正交反应的同时，温和、直接且操作简便地形成具有药物相关性的碳-碳键。含氮杂环化合物对人类健康产生了深远影响，因为这些化学基元存在于大量用于对抗广泛疾病和病理生理条件的药物中。过渡金属介导的交叉偶联的进展简化了这些分子的合成；然而，不依赖预官能化起始材料的具有药物重要性的杂环的碳氢官能化是一个发展不足的领域。不幸的是，杂环的天生特性使其在生物应用中如此受欢迎，例如水溶性和作为配体的能力，这使得它们成为直接化学官能化的具有挑战性的底物。在这里，我们报道亚磺酸锌盐可用于将烷基自由基转移到杂环上，从而在与其他固有的碳氢官能化方法互补反应的同时，温和（中温，50°C或更低）、直接且操作简便地形成具有药物相关性的碳-碳键。我们准备了一套这些试剂，并在不借助于保护基化学的情况下，研究了它们在广泛的杂环（天然产物、药物和构建块）中的反应性。这些试剂甚至可以在有水和空气的情况下单锅串联使用。
• Photoredox-catalyzed direct C–H monofluoromethylation of heteroarenes
  作者：Nagarajan Ramkumar、Ketrina Plantus、Melita Ozola、Anatoly Mishnev、Vizma Nikolajeva、Maris Senkovs、Maksim Ošeka、Janis Veliks

  DOI：10.1039/d3nj04313d

  日期：——

  an iodine(III) reagent containing monofluoroacetoxy ligands can be used to transfer monofluoromethyl radicals to heterocycles via visible-light photoredox catalysis, allowing for the mild, direct, and operationally simple modification of medicinally relevant heterocycles through a Minisci-like C–H functionalization process. This approach enriches the synthesis of a structurally diverse set of heteroaromatics

  氟烷基在医药产品和农用化学品中发挥着至关重要的作用，将它们安装到芳基和杂环上通常可以增强理化和生物特性。其中，含有单氟甲基的杂环是一类颇具吸引力但很少研究的有机氟化合物，在药物化学中具有潜在的应用前景。在这里，我们报道了含有单氟乙酰氧基配体的碘（III）试剂可用于通过可见光光氧化还原催化将单氟甲基自由基转移至杂环，从而允许通过类似Minisci的C对医学相关的杂环进行温和、直接且操作简单的修饰–H 功能化过程。这种方法以中等至优异的产率丰富了包含单氟甲基的结构多样的杂芳族化合物的合成。还证明了直接 C-H 自由基单氟甲基化用于医学相关生物分子和药物后期修饰的实用性。此外，单氟甲基化杂环化合物表现出有前景的抗菌和抗癌活性，表明该方法可能有助于药物发现，作为新小分子药物开发中先导药物修饰的可靠工具。
• Inexpensive Radical Methylation and Related Alkylations of Heteroarenes
  作者：Qi Huang、Samir Z. Zard

  DOI：10.1021/acs.orglett.8b00190

  日期：2018.3.2

  A simple method for the introduction of a methyl and higher aliphatic group to various heteroarenes using very inexpensive reagents is described. It is based on the radical addition of a carboxylic xanthate followed by decarboxylation. Depending on the heteroarene structure, the decarboxylation can be spontaneous or induced by heating in N,N-dimethylacetamide or N-methyl pyrrolidone in a microwave

  描述了一种使用非常便宜的试剂将甲基和高级脂肪族基团引入各种杂芳烃的简单方法。它基于羧酸黄原酸酯的自由基加成，然后进行脱羧。取决于杂芳烃结构，脱羧可以是自发的，或者可以通过在微波炉中的N，N-二甲基乙酰胺或N-甲基吡咯烷酮中加热来引发。