(R)-6-cyclopentyl-6-(2-(2,6-diethylpyridin-4-yl)ethyl)-dihydro-2H-pyran-2,4(3H)-dione | 927889-49-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: (R)-6-cyclopentyl-6-(2-(2,6-diethylpyridin-4-yl)ethyl)-dihydro-2H-pyran-2,4(3H)-dione
• 英文别名: (R)-6-cyclopentyl-6-(2-(2,6-diethylpyridin-4-yl)ethyl)-dihyro-2H-pyran-2,4(3H)-dione；(R)-6-cyclopentyl-6-(2,6-diethylpyridin-4-yl)ethyl-4-hydroxy-5,6-dihydropyran-2-one；(2R)-2-cyclopentyl-2-[2-(2,6-diethylpyridin-4-yl)ethyl]-4-hydroxy-3H-pyran-6-one
• CAS: 927889-49-4
• 化学式: C₂₁H₂₉NO₃
• 分子量: 343.466
• InChiKey: XWJTVDVZEWHAPD-OAQYLSRUSA-N

物化性质

• 沸点：
  503.8±50.0 °C(Predicted)
• 密度：
  1.144±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-6-cyclopentyl-6-(2-(2,6-diethylpyridin-4-yl)ethyl)-dihydro-2H-pyran-2,4(3H)-dione 、 D-二苯甲酰酒石酸 以 二氯甲烷 、 甲基叔丁基醚 为溶剂， 反应 1.0h， 生成 dibenzoyl-D-tartaric acid salt of (R)-6-cyclopentyl-6-(2,6-diethylpyridin-4-yl)ethyl-4-hydroxy-5,6-dihydropyran-2-one
  参考文献：
  名称：

  WO2007/23381

  摘要：

  公开号：
• 作为产物：
  描述：

  环戊基甲酰氯 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 甲烷磺酸 、 palladium 10% on activated carbon 、 氢气 、 碳酸氢钠 、 三乙胺 、 N,N-二异丙基乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 水 、 异丙醇 、 甲苯 为溶剂， -85.0~45.0 ℃ 、446.08 kPa 条件下， 反应 11.81h， 生成 (R)-6-cyclopentyl-6-(2-(2,6-diethylpyridin-4-yl)ethyl)-dihydro-2H-pyran-2,4(3H)-dione
  参考文献：
  名称：

  Synthesis of Filibuvir. Part I. Diastereoselective Preparation of a β-Hydroxy Alkynyl Oxazolidinone and Conversion to a 6,6-Disubstituted 2H-Pyranone

  摘要：

  This is the first in a series of three papers describing the identification and development of a commercial synthesis of filibuvir (1). This contribution describes development of an Evans aldol reaction to control the tertiary alcohol stereocenter, a challenging variant of that strategy in that both reacting partners were nonstandard (acetate etiolate and ketone electrophile). A sequence consisting of Sonogashira coupling, acylation and hydrogenation delivered acetate 24, and Dieckmann cyclization provided beta-keto lactone 2.

  DOI：

  10.1021/op4002356

文献信息

• Synthesis of Filibuvir. Part II. Second-Generation Synthesis of a 6,6-Disubstituted 2<i>H</i>-Pyranone via Dieckmann Cyclization of a β-Acetoxy Ester
  作者：Zhihui Peng、John A. Ragan、Roberto Colon-Cruz、Brian G. Conway、Eric M. Cordi、Kyle Leeman、Leo J. Letendre、Li-Jen Ping、Janice E. Sieser、Robert A. Singer、Gregory W. Sluggett、Holly Strohmeyer、Brian C. Vanderplas、Jon Blunt、Nicola Mawby、Kevin Meldrum、Stuart Taylor

  DOI：10.1021/op400236r

  日期：2014.1.17

  drivers behind this change were the modest and variable yields observed in the intramolecular cyclization to generate the β-keto lactone. Changing the cyclization substrate from oxazolidinone to alkyl ester offered a significantly improved cyclization, as well as improvements in the alkyne hydrogenation. Selection of the optimal substrates for methanolysis and intermediate salt formation are also described

  本文描述了将恶唑烷酮（3）转化为β-酮内酯（5）的改进顺序。引起这一变化的主要驱动力是在分子内环化反应中产生β-酮内酯时观察到适度和可变的产率。将环化底物从恶唑烷酮改为烷基酯可显着改善环化作用，并改善炔烃加氢反应。还描述了用于甲醇分解和形成中间盐的最佳底物的选择。
• Synthesis of Filibuvir. Part III. Development of a Process for the Reductive Coupling of an Aldehyde and a β-Keto-lactone
  作者：Nathan D. Ide、John. A. Ragan、Gabriel Bellavance、Steve J. Brenek、Eric M. Cordi、Grace O. Jensen、Kris N. Jones、Danny LaFrance、Kyle R. Leeman、Leo J. Letendre、David Place、Corey L. Stanchina、Gregory W. Sluggett、Holly Strohmeyer、Jon Blunt、Kevin Meldrum、Stuart Taylor、Ciaran Byrne、Denis Lynch、Sandra Mullane、Maria M. O’Sullivan、Marcella Whelan

  DOI：10.1021/op400237j

  日期：2014.1.17

  Development of a reductive coupling of a β-keto-lactone and an aldehyde is described, in which the Hantzsch ester serves as an inexpensive and convenient reducing agent. Structural features in the β-keto-lactone rendered standard reductive coupling conditions ineffective, requiring development of a specific addition and temperature protocol. Identification of one of the reactants as Ames positive required

  描述了β-酮内酯与醛的还原偶联的开发，其中汉茨tz酯用作便宜且方便的还原剂。β-酮-内酯的结构特征使标准的还原偶联条件无效，需要开发特定的添加和温度方案。要确定一种反应物为Ames阳性，就需要对最终活性药物成分（API）中的这种杂质采用百万分之几的控制策略。
• METHODS FOR THE PREPARATION OF HCV POLYMERASE INHIBITORS
  申请人：Matthews Christopher Frederick

  公开号：US20090023921A1

  公开（公告）日：2009-01-22

  The present invention relates to methods and compounds useful in the preparation of compounds of the formula (I).

  本发明涉及用于制备式(I)化合物的方法和化合物。
• Methods for the Preparation of HCV Polymerase Inhibitors
  申请人：Matthews Christopher Frederick

  公开号：US20110070187A1

  公开（公告）日：2011-03-24

  The present invention relates to methods and compounds useful in the preparation of compounds of the formula (I).

  本发明涉及用于制备式(I)化合物的方法和化合物。
• Org. Process Res. Dev. 2014, 18, 36-44
  作者：

  DOI：——

  日期：——