1-(4-methoxybenzyl)-5-chloro-3-(2-phenylethynyl)pyrazin-2(1H)-one | 1011736-18-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-(4-methoxybenzyl)-5-chloro-3-(2-phenylethynyl)pyrazin-2(1H)-one
• 英文别名: 1-(4-methoxybenzyl)-5-chloro-3-(phenylethynyl)pyrazin-2(1H)-one；5-chloro-1-(4-methoxybenzyl)-3-(phenylethynyl)pyrazin-2(1H)-one；5-Chloro-1-[(4-methoxyphenyl)methyl]-3-(2-phenylethynyl)pyrazin-2-one
• CAS: 1011736-18-7
• 化学式: C₂₀H₁₅ClN₂O₂
• 分子量: 350.804
• InChiKey: KNHTXEVIODCAKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  41.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-methoxybenzyl)-5-chloro-3-(2-phenylethynyl)pyrazin-2(1H)-one 在 bis(3-methyl-2,3-dihydro-benzothiazole-2-ylidene) palladium(II) diiodide 、 四丁基溴化铵 、 碘 、 palladium diacetate 、 caesium carbonate 、 三乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 20.0~140.0 ℃ 、800.01 kPa 条件下， 反应 2.75h， 生成 methyl 2-acetamido-6-phenylfuro[3,2-b]pyrazine-7-carboxylate
  参考文献：
  名称：

  Synthesis of functionalized furopyrazines as restricted dipeptidomimetics

  摘要：

  Herein, an efficient synthetic approach to a furopyrazine scaffold with four points of diversity, starting from 2(1H)-pyrazinones, with dipeptomimetic properties, is presented. R-groups corresponding to amino acid side chains were introduced during the 2(1H)-pyrazinone and subsequent furopyrazine formation. The furopyrazine scaffold was further functionalized with an amino- and a carboxy-terminus resulting in a conformationally restricted dipeptidomimetic scaffold. The carboxy-terminus was introduced via a chemoselective vinylation of the 7-position followed by oxidative cleavage, while the amino-terminus was obtained via Buchwald-Hartwig amidation of the 2-position of the scaffold. The versatility of the synthetic method was demonstrated by the synthesis of a small library of diversely substituted furopyrazines having various amino acid side chains on the four points of diversity. Evaluation with an X-ray structure of the scaffold and computational analysis supports the exploitation of the furopyrazine scaffold as a restricted dipeptide mimic, which can mimic the two central residues of a beta-turn. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2012.02.022
• 作为产物：
  描述：

  magnesium,ethynylbenzene,bromide 、 5-chloro-1-(4-methoxybenzyl)-3-(phenylsulfanyl)pyrazin-2(1H)-one 在 三(2-呋喃基)膦 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 为溶剂， 以89%的产率得到1-(4-methoxybenzyl)-5-chloro-3-(2-phenylethynyl)pyrazin-2(1H)-one
  参考文献：
  名称：

  通过脱硫熊田型交叉偶联反应，温和的室温钯催化2（1 H）-吡嗪酮的C3-芳构化†

  摘要：

  一个有效的脱硫Kumada型交叉耦合协议已报告为5-氯-3-（苯基硫烷基）吡嗪-2（1 H）-ones的C3-芳基化。该方法也已成功地扩展到某些（杂）芳基硫醚和硫酯的芳基化反应。

  DOI：

  10.1021/jo901327y

文献信息

• Ag⁺-Mediated Synthesis of Substituted Furo[2,3-<i>b</i>]pyrazines
  作者：Erik Van der Eycken、Denis Ermolat’ev、Vaibhav Mehta

  DOI：10.1055/s-2007-992358

  日期：——

  A highly efficient method for the preparation of trisubstituted furo[2,3-b]pyrazines has been developed. Sonogashira coupling reaction with the readily available 1-(4-methoxybenzyl)-3,5-dichloropyrazin-2(1H)-ones was followed by silver-catalyzed heteroannulation to provide the corresponding 2-chlorofuro[2,3-b]pyrazines in excellent yields. The latter were subjected to Suzuki or Buchwald-Hartwig coupling reaction for further decoration.

  开发了一种制备三取代呋喃并[2,3-b]吡嗪的高效方法。首先使用易于获得的1-(4-甲氧基苄基)-3,5-二氯吡嗪-2(1H)-酮进行Sonogashira偶联反应，随后通过银催化的杂环化作用，以优异的产率得到了相应的2-氯呋喃并[2,3-b]吡嗪。后者再通过Suzuki或Buchwald-Hartwig偶联反应进行进一步修饰。
• The First Palladium-Catalyzed Desulfitative Sonogashira-Type Cross-Coupling of (Hetero)aryl Thioethers with Terminal Alkynes
  作者：Vaibhav Pravinchandra Mehta、Anuj Sharma、Erik Van der Eycken

  DOI：10.1021/ol800054b

  日期：2008.3.1

  An unprecedented desulfitative Sonogashira-type cross-coupling protocol is exemplified by the synthesis of substituted 5-chloro-3-alkynylpyrazinones from the corresponding 5-chloro-3-(phenylsulfanyl) pyrazin-2(1H)-ones. The applicability of the method is extended to solid-phase linked pyrazin-2(1H)-ones as well as to some oxazinones, pyrazines, and phenyl thioesters.

  由相应的5-氯-3-（苯基硫烷基）吡嗪-2（1H）-酮合成取代的5-氯-3-炔基吡嗪酮类化合物，说明了空前的脱硫Sonogashira型交叉偶联方案。该方法的适用范围扩展到固相连接的吡嗪-2（1H）-酮以及一些恶嗪酮，吡嗪和苯基硫代酯。
• Mild Room-Temperature Palladium-Catalyzed C3-Arylation of 2(1<i>H</i>)-Pyrazinones via a Desulfitative Kumada-Type Cross-Coupling Reaction
  作者：Vaibhav P. Mehta、Sachin G. Modha、Erik Van der Eycken

  DOI：10.1021/jo901327y

  日期：2009.9.4

  An efficient desulfitative Kumada-type cross-coupling protocol is reported for the C3-arylation of 5-chloro-3-(phenylsulfanyl)pyrazin-2(1H)-ones. The method has also been successfully extended to the arylation of some (hetero)aryl thioethers and thioesters.

  一个有效的脱硫Kumada型交叉耦合协议已报告为5-氯-3-（苯基硫烷基）吡嗪-2（1 H）-ones的C3-芳基化。该方法也已成功地扩展到某些（杂）芳基硫醚和硫酯的芳基化反应。
• Synthesis of functionalized furopyrazines as restricted dipeptidomimetics
  作者：Stijn Claerhout、Sweta Sharma、Christian Sköld、Claudia Cavaluzzo、Anja Sandström、Mats Larhed、Meganathan Thirumal、Virinder S. Parmar、Erik V. Van der Eycken

  DOI：10.1016/j.tet.2012.02.022

  日期：2012.4

  Herein, an efficient synthetic approach to a furopyrazine scaffold with four points of diversity, starting from 2(1H)-pyrazinones, with dipeptomimetic properties, is presented. R-groups corresponding to amino acid side chains were introduced during the 2(1H)-pyrazinone and subsequent furopyrazine formation. The furopyrazine scaffold was further functionalized with an amino- and a carboxy-terminus resulting in a conformationally restricted dipeptidomimetic scaffold. The carboxy-terminus was introduced via a chemoselective vinylation of the 7-position followed by oxidative cleavage, while the amino-terminus was obtained via Buchwald-Hartwig amidation of the 2-position of the scaffold. The versatility of the synthetic method was demonstrated by the synthesis of a small library of diversely substituted furopyrazines having various amino acid side chains on the four points of diversity. Evaluation with an X-ray structure of the scaffold and computational analysis supports the exploitation of the furopyrazine scaffold as a restricted dipeptide mimic, which can mimic the two central residues of a beta-turn. (C) 2012 Elsevier Ltd. All rights reserved.