(S)-2-[(S)-(2,4-dinitrophenoxy)phenoxy(phosphoryl)amino]propionic acid isopropyl ester | 1334513-00-6

• 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: (S)-2-[(S)-(2,4-dinitrophenoxy)phenoxy(phosphoryl)amino]propionic acid isopropyl ester
• 英文别名: propan-2-yl (2S)-2-[[(2,4-dinitrophenoxy)-phenoxyphosphoryl]amino]propanoate
• CAS: 1334513-00-6
• 化学式: C₁₈H₂₀N₃O₉P
• 分子量: 453.345
• InChiKey: GREAMYRMNGJYSF-FYKVGYICSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  166
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (S)-2-[(S)-(2,4-dinitrophenoxy)phenoxy(phosphoryl)amino]propionic acid isopropyl ester 、 2',3'-异丙叉腺苷 在 叔丁基氯化镁 作用下， 以 四氢呋喃 为溶剂， 反应 0.55h， 生成 isopropyl ((S)-(((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methoxy)(phenoxy)phosphoryl)-L-alaninate
  参考文献：
  名称：

  Synthesis of Diastereomerically Pure Nucleotide Phosphoramidates

  摘要：

  Prodrugs of therapeutic nucleoside monophosphates masked as phosphoramidate derivatives have become an increasingly important class of antiviral drugs in pharmaceutical research for delivering nucleotides in vitro and in vivo. Conventionally, phosphoramidate derivatives are prepared as a mixture of two diastereomers. We report a class of stable phosphoramidating reagents containing an amino acid ester and two phenolic groups, one unsubstituted and the other with electron-withdrawing substituents. The reagents can be isolated as single diastereomers and reacted with the 5'-hydroxyl group of nucleosides through selective nucleophilic displacement of the substituted phenol to prepare single diastereomer phosphoramidate products. This method has been used to prepare the HCV clinical candidate PSI-7977 in high yield and high diastereomeric purity.

  DOI：

  10.1021/jo201492m
• 作为产物：
  描述：

  二氯磷酸苯酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (S)-2-[(S)-(2,4-dinitrophenoxy)phenoxy(phosphoryl)amino]propionic acid isopropyl ester
  参考文献：
  名称：

  Synthesis of Diastereomerically Pure Nucleotide Phosphoramidates

  摘要：

  Prodrugs of therapeutic nucleoside monophosphates masked as phosphoramidate derivatives have become an increasingly important class of antiviral drugs in pharmaceutical research for delivering nucleotides in vitro and in vivo. Conventionally, phosphoramidate derivatives are prepared as a mixture of two diastereomers. We report a class of stable phosphoramidating reagents containing an amino acid ester and two phenolic groups, one unsubstituted and the other with electron-withdrawing substituents. The reagents can be isolated as single diastereomers and reacted with the 5'-hydroxyl group of nucleosides through selective nucleophilic displacement of the substituted phenol to prepare single diastereomer phosphoramidate products. This method has been used to prepare the HCV clinical candidate PSI-7977 in high yield and high diastereomeric purity.

  DOI：

  10.1021/jo201492m

文献信息

• [EN] PROCESS FOR THE PREPARATION OF (Sp)-SOFOSBUVIR AND INTERMEDIATES THEREOF<br/>[FR] PROCÉDÉ DE PRÉPARATION DU (SP)-SOFOSBUVIR ET DE SES INTERMÉDIAIRES
  申请人：ALEMBIC PHARMACEUTICALS LTD

  公开号：WO2018025195A1

  公开（公告）日：2018-02-08

  The present invention is directed towards process for preparation of an optically pure (Sp)-Sofosbuvir of Formula-(I) and its intermediate namely (Sp)-isomer of isopropyl alanyl phosphoramidate of Formula (III) thereof.

  本发明涉及一种制备光学纯(Sp)-索非布韦（化学式(I)）及其中间体即异丙基丙氨基磷酰胺的(Sp)-异构体（化学式(III)）的方法。
• [EN] PURINE NUCLEOSIDE PHOSPHORAMIDATE<br/>[FR] PHOSPHORAMIDATE DE NUCLÉOSIDE DE TYPE PURINE
  申请人：PHARMASSET INC

  公开号：WO2011123672A1

  公开（公告）日：2011-10-06

  Disclosed herein is a compound represented by formula 1 or its hydrate thereof in crystalline or crystal-like form.

  本文披露了一种由公式1表示的化合物或其水合物，以结晶或类晶体形式存在的化合物。
• STEREOSELECTIVE SYNTHESIS OF PHOSPHORUS CONTAINING ACTIVES
  申请人：ROSS BRUCE S.

  公开号：US20110245484A1

  公开（公告）日：2011-10-06

  Disclosed herein are phosphorus-containing actives, their use as actives for treating diseases, and a stereoselective process for preparing the same. Also disclosed herein are useful synthetic intermediates and processes for preparing the same.

  本文披露了含磷活性物质，其作为治疗疾病的活性物质的用途，以及用于制备它们的立体选择性过程。本文还披露了有用的合成中间体和制备它们的过程。
• PURINE NUCLEOSIDE PHOSPHORAMIDATE
  申请人：CHANG WONSUK

  公开号：US20110257121A1

  公开（公告）日：2011-10-20

  Disclosed herein is a compound represented by formula 1 or its hydrate thereof in crystalline or crystal-like form.

  本文揭示了一种由公式1所表示的化合物或其水合物的晶体或类晶体形式。
• Stereoselective synthesis of phosphorus containing actives
  申请人：Gilead Pharmasset LLC

  公开号：EP2752422A1

  公开（公告）日：2014-07-09

  Disclosed herein is a process for preparing an enantiomerically- or a diastereomerically enriched phosphorus-containing active, salt, or pharmaceutically acceptable salt thereof, of formula I-1 , which comprises the steps of: (a) reacting a protected or unprotected Active with a base to form a salt of said active and then reacting said salt with an enantiomerically- or a diastereomerically enriched compound of formula II-1 wherein the Active is a nucleoside, a nucleoside-analog, or a non-nucleoside.

  本文公开了一种制备式 I-1 的对映体或非对映异构体富集的含磷活性物质、盐或其药学上可接受的盐的方法 ，其步骤包括(a) 使受保护或未受保护的活性物质与碱反应，形成所述活性物质的盐，然后使所述盐与富含对映体或非对映异构体的式 II-1 化合物反应； (b) 使受保护或未受保护的活性物质与碱反应，形成所述活性物质的盐，然后使所述盐与富含对映体或非对映异构体的式 II-1 化合物反应。 其中活性物质为核苷、核苷类似物或非核苷。