6-iodo-1-(prop-2-yn-1-yl)pyridin-2(1H)-one | 173442-38-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 6-iodo-1-(prop-2-yn-1-yl)pyridin-2(1H)-one
• 英文别名: N-propargyl-6-iodopyridone；6-iodo-1-prop-2-ynylpyridin-2-one
• CAS: 173442-38-1
• 化学式: C₈H₆INO
• 分子量: 259.046
• InChiKey: GZJICCUUZMWBKU-UHFFFAOYSA-N

物化性质

• 沸点：
  339.9±42.0 °C(Predicted)
• 密度：
  1.88±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  6-iodo-1-(prop-2-yn-1-yl)pyridin-2(1H)-one 在 氢溴酸 、 六甲基二锡 作用下， 以 乙酸乙酯 、 苯 为溶剂， 反应 23.0h， 生成 3-fluoro-11H-indolizino[1,2-b]quinolin-9-one
  参考文献：
  名称：

  A General Synthetic Approach to the (20S)-Camptothecin Family of Antitumor Agents by a Regiocontrolled Cascade Radical Cyclization of Aryl Isonitriles

  摘要：

  A general and efficient synthesis of (20S)-camptothecin (1a) is reported. A key common intermediate containing the pyridone and lactone (DE) rings of camptothecin and most derivatives was constructed from 2-trimethylsilyl-6-methoxypyridine by a series of metalation reactions and a Heck cyclization to provide an achiral bicyclic enol ether. Sharpless asymmetric dihydroxylation followed by lactol oxidation and iododesilylation produced the key intermediate in 94% enantiomeric excess. Alkylation with propargyl bromide and a cascade radical reaction with phenyl isonitrile then produced 1a. About 20 other penta- and hexacyclic analogues of camptothecin with differing single or multiple substituents at C7, C9, C10, C11, and/or C12 were made by changing the propargylating agent and the isonitrile. Included among these are several drug candidates and the approved drugs topotecan and irinotecan. The synthesis of the prodrug irinotecan is direct one that does not pass through the active metabolite. The use of ortho-trimethylsilyl-substituted isonitriles allows the regioselective synthesis of camptothecin analogues in cases where isomeric mixtures are formed from the parent isonitriles. The synthesis of the derivatives relies on the broad scope and functional group tolerance of the key cascade radical reaction.

  DOI：

  10.1002/(sici)1521-3765(199801)4:1<67::aid-chem67>3.0.co;2-f
• 作为产物：
  描述：

  2-碘-6-甲氧基吡啶 在 三甲基氯硅烷 、 sodium hydride 、 sodium iodide 作用下， 以 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 17.67h， 生成 6-iodo-1-(prop-2-yn-1-yl)pyridin-2(1H)-one
  参考文献：
  名称：

  可见光诱导的自由基级联环化：喜树碱的ABCD环核的合成。

  摘要：

  从易得的异氰基芳烃和N-（烷基-2-yn-1-基）吡啶-2（n）合成吲哚并[1,2 - b ]喹啉9（11 H）-（喜树碱的环核）的新策略已经通过可见光诱导的自由基级联环化过程开发了1 H）-one。反应在温和的条件下进行，产率中等至优异。容易为两种反应物引入取代基以及反应对官能团的宽容度使其成为通向喜树碱及其衍生物核心的直接途径。

  DOI：

  10.1021/acs.joc.7b03283

文献信息

• Tandem radical reactions of isonitriles with 2-pyridonyl and other aryl radicals: Scope and limitations, and a first generation synthesis of (±)-camptothecin
  作者：Dennis P. Curran、Hui Liu、Hubert Josien、Sung-Bo Ko

  DOI：10.1016/0040-4020(96)00633-3

  日期：1996.8

  isonitriles provides tetra- and penta-cyclic products in a single step by a sequence of radical addition to the isonitrile followed by two cyclizations. The scope and limitations of the process are described along with a first generation synthesis of racemic camptothecin.

  在芳基异腈存在下，对N-炔丙基-6-卤代-2-吡啶酮和相关的芳族卤化物进行光解可通过一步向异腈中进行一系列自由基加成，然后进行两次环化，一步即可提供四环和五环产物。描述了该方法的范围和局限性以及外消旋喜树碱的第一代合成方法。
• Cascade 4+1 Radical Annulations of 2,6-Disubstituted Phenyl Isonitriles with <i>N</i>-Propargyl-6-Iodopyridones: Scope, Mechanism and Regioselective Synthesis of 7,9-Disubstituted Camptothecin Analogs
  作者：Dennis Curran、Wu Du

  DOI：10.1055/s-2003-40327

  日期：——

  The reaction of o,o′-dialkyl-substituted aryl isonitriles with N-propargyl-6-iodopyridones provides 11H-indolizino[1,2-b]quinolin-9-ones with significant regioselectivity in favor of the more crowded product. The usefulness of the method is illustrated with a regioselective synthesis of (20S)-7-trimethylsilyl-9-isopropyl camptothecin.

  o,o'-二烷基取代的芳基异腈与 N-propargyl-6-iodopyridones 的反应提供了具有显着区域选择性的 11H-indolizino[1,2-b]quinolin-9-ones，有利于更拥挤的产物。该方法的有用性通过 (20S)-7-三甲基甲硅烷基-9-异丙基喜树碱的区域选择性合成来说明。
• Selective N-functionalization of 6-substituted-2-pyridones
  作者：Hui Liu、Sung-Bo Ko、Hubert Josien、Dennis P. Curran

  DOI：10.1016/0040-4039(95)01917-7

  日期：1995.12

  6-Substituted-2-pyridones can be selectively N-alkylated by treatment with NaH/LiBr in a mixture of DMF and DME. Yields of N-propargylated, N-allylated, and other N-functionalized products are good, and only small amounts of the isomeric O-alkylated product (<10%) are typically formed.