(2S,4R)-4-((4-allylisoindoline-2-carbonyl)oxy)-1-((S)-2-((((2,2-dimethylpent-4-en-1-yl)oxy)carbonyl ) amino)-3 ,3-dimethylbutanoyl)pyrrolidine-2-carboxylic acid | 1372882-64-8

• 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: (2S,4R)-4-((4-allylisoindoline-2-carbonyl)oxy)-1-((S)-2-((((2,2-dimethylpent-4-en-1-yl)oxy)carbonyl ) amino)-3 ,3-dimethylbutanoyl)pyrrolidine-2-carboxylic acid
• 英文别名: (2S,4R)-1-[(2S)-2-(2,2-dimethylpent-4-enoxycarbonylamino)-3,3-dimethylbutanoyl]-4-(4-prop-2-enyl-1,3-dihydroisoindole-2-carbonyl)oxypyrrolidine-2-carboxylic acid
• CAS: 1372882-64-8
• 化学式: C₃₁H₄₃N₃O₇
• 分子量: 569.698
• InChiKey: JVZOIBPRFRUCPQ-PZUNEJSGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  41
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  126
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S,4R)-4-((4-allylisoindoline-2-carbonyl)oxy)-1-((S)-2-((((2,2-dimethylpent-4-en-1-yl)oxy)carbonyl ) amino)-3 ,3-dimethylbutanoyl)pyrrolidine-2-carboxylic acid 在 Hoveyda-Grubbs catalyst second generation 、 2,6-二氯-1,4-苯醌 、 5%-palladium/activated carbon 、 氢气 作用下， 以 异丙醇 、 甲苯 为溶剂， 100.0 ℃ 、310.27 kPa 条件下， 反应 24.0h， 生成 (1R,21S,24S)-21-tert-butyl-16,16-dimethyl-3,19,22-trioxo-2,18-dioxa-4,20,23-triazatetracyclo[21.2.1.1(4,7).0(6,11)]heptacosa-6,8,10-triene-24-carboxylic acid
  参考文献：
  名称：

  Synthesis of the HCV Protease Inhibitor Vaniprevir (MK-7009) Using Ring-Closing Metathesis Strategy

  摘要：

  A highly efficient synthesis of Vaniprevir (MK-7009) has been accomplished in nine linear steps and 55% overall yield. The key features of this synthesis include a cost-effective synthesis of the isoindoline subunit and efficient construction of the 20-membered macrocyclic core of Vaniprevir (MK-7009) utilizing ring-closing metathesis technology. A high-performing ring-closing metathesis protocol has been achieved by simultaneous slow addition of the ruthenium catalyst (0.2 mol %) and the diene substrate at a concentration of 0.13 M.

  DOI：

  10.1021/jo3001595
• 作为产物：
  描述：

  2,2-dimethylpent-4-en-1-ol 在 吡啶 、 水 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N'-羰基二咪唑 、 柠檬酸 、 potassium hydroxide 作用下， 以 N,N-二甲基甲酰胺 、 异丙醇 、 甲苯 、 乙腈 为溶剂， 反应 39.0h， 生成 (2S,4R)-4-((4-allylisoindoline-2-carbonyl)oxy)-1-((S)-2-((((2,2-dimethylpent-4-en-1-yl)oxy)carbonyl ) amino)-3 ,3-dimethylbutanoyl)pyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  Synthesis of the HCV Protease Inhibitor Vaniprevir (MK-7009) Using Ring-Closing Metathesis Strategy

  摘要：

  A highly efficient synthesis of Vaniprevir (MK-7009) has been accomplished in nine linear steps and 55% overall yield. The key features of this synthesis include a cost-effective synthesis of the isoindoline subunit and efficient construction of the 20-membered macrocyclic core of Vaniprevir (MK-7009) utilizing ring-closing metathesis technology. A high-performing ring-closing metathesis protocol has been achieved by simultaneous slow addition of the ruthenium catalyst (0.2 mol %) and the diene substrate at a concentration of 0.13 M.

  DOI：

  10.1021/jo3001595

文献信息

• PROCESS AND INTERMEDIATES FOR PREPARING MACROLACTAMS
  申请人：Chen Cheng

  公开号：US20130274463A1

  公开（公告）日：2013-10-17

  The present invention relates to macrolactam compounds, intermediates useful in the preparation of macrolactams, methods for preparing the intermediates, and methods for preparing and modifying macrolactams. One use of the compounds and methods described herein is in the production of macrolactam compounds able to inhibit HCV NS3 protease activity. An example of an HCV inhibitory compound that can be synthesized using the procedures described herein is Compound A and derivative thereof.

  本发明涉及大环内酰胺化合物，用于制备大环内酰胺的中间体，制备中间体的方法，以及制备和改性大环内酰胺的方法。本文描述的化合物和方法之一是用于生产能够抑制HCV NS3蛋白酶活性的大环内酰胺化合物。可以使用本文描述的程序合成HCV抑制化合物的例子是化合物A及其衍生物。
• US9120818B2
  申请人：——

  公开号：US9120818B2

  公开（公告）日：2015-09-01
• [EN] PROCESS AND INTERMEDIATES FOR PREPARING MACROLACTAMS<br/>[FR] PROCÉDÉ ET INTERMÉDIAIRES POUR LA PRÉPARATION DE MACROLACTAMES
  申请人：MERCK SHARP & DOHME

  公开号：WO2012082672A2

  公开（公告）日：2012-06-21

  The present invention relates to macrolactam compounds, intermediates useful in the preparation of macrolactams, methods for preparing the intermediates, and methods for preparing and modifying macrolactams. One use of the compounds and methods described herein is in the production of macrolactam compounds able to inhibit HCV NS3 protease activity. An example of an HCV inhibitory compound that can be synthesized using the procedures described herein is Compound A and derivative thereof.
• Synthesis of the HCV Protease Inhibitor Vaniprevir (MK-7009) Using Ring-Closing Metathesis Strategy
  作者：Jongrock Kong、Cheng-yi Chen、Jaume Balsells-Padros、Yang Cao、Robert F. Dunn、Sarah J. Dolman、Jacob Janey、Hongmei Li、Michael J. Zacuto

  DOI：10.1021/jo3001595

  日期：2012.4.20

  A highly efficient synthesis of Vaniprevir (MK-7009) has been accomplished in nine linear steps and 55% overall yield. The key features of this synthesis include a cost-effective synthesis of the isoindoline subunit and efficient construction of the 20-membered macrocyclic core of Vaniprevir (MK-7009) utilizing ring-closing metathesis technology. A high-performing ring-closing metathesis protocol has been achieved by simultaneous slow addition of the ruthenium catalyst (0.2 mol %) and the diene substrate at a concentration of 0.13 M.