N-(5-((Z)-2-((2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxotetrahydro-2H-pyran-2-yl)vinyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide | 1246665-84-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N-(5-((Z)-2-((2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxotetrahydro-2H-pyran-2-yl)vinyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide
• 英文别名: N-[5-[(Z)-2-[(2S,4R)-4-[tert-butyl(dimethyl)silyl]oxy-6-oxooxan-2-yl]ethenyl]-4-(4-fluorophenyl)-6-propan-2-ylpyrimidin-2-yl]-N-methylmethanesulfonamide
• CAS: 1246665-84-8
• 化学式: C₂₈H₄₀FN₃O₅SSi
• 分子量: 577.793
• InChiKey: WZGPIBBCDYPFDI-IEHPJGJUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.91
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  107
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-(5-((Z)-2-((2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxotetrahydro-2H-pyran-2-yl)vinyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide 在 溶剂黄146 、 tetra-n-butylammoniumfluoride trihydrate 作用下， 以 四氢呋喃 为溶剂， 反应 22.0h， 以55%的产率得到N-(4-(4-fluorophenyl)-5-((Z)-2-((2S,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl)vinyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide
  参考文献：
  名称：

  Conformational analysis of E/Z-isomeric pairs of rosuvastatin and its lactonized analogues

  摘要：

  Most of the super-statins contain a C=C double bond spacer between the heterocyclic and the chiral dihydroxycarboxylic moieties. The known drugs are E-geometric isomers, whereas very little is known about their Z-isomeric analogues. This study explains the unusual resonance line broadening observed in 1H NMR spectra of Z-isomeric rosuvastatin analogues at room temperature, which originates from dynamic exchange between different conformers. Conformational equilibria and intrinsic preferences of Z-isomeric rosuvastatin analogues provide valuable insight into conformational variability that is important for studying potential interactions within the binding site of the enzyme. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2013.05.020
• 作为产物：
  描述：

  (4R,6S)-4-(tert-butyldimethylsilyloxy)-6-(dihydroxymethyl)tetrahydro-2H-pyran-2-one 、 N-[4-(4-fluorophenyl)-6-propan-2-yl-5-[(tributyl-lambda5-phosphanylidene)methyl]pyrimidin-2-yl]-N-methylmethanesulfonamide 以 甲苯 为溶剂， 生成 N-(5-{(E)-2-[(2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxotetrahydro-2H-pyran-2-yl]vinyl}-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide 、 N-[4-(4-氟苯基)-5-甲基-6-(1-甲基乙基)-2-嘧啶基]-N-甲基甲烷磺酰胺 、 N-(5-((Z)-2-((2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxotetrahydro-2H-pyran-2-yl)vinyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide
  参考文献：
  名称：

  利用维蒂希反应的他汀类药物的内酯途径。罗苏伐他汀的合成

  摘要：

  据报道，他汀类药物通过内酯化侧链首次进入，以罗苏伐他汀的合成为例。关键步骤是将（2 S，4 R）-4-（叔丁基二甲基甲硅烷氧基）-6-氧四氢-2 H-吡喃-2-甲醛与适当官能化的嘧啶杂环的phospho盐进行Wittig偶联。一锅脱保护和水解所得4- O- TBS罗苏伐他汀内酯以高收率提供罗苏伐他汀。

  DOI：

  10.1021/jo101050z

文献信息

• Lactone Pathway to Statins Utilizing the Wittig Reaction. The Synthesis of Rosuvastatin
  作者：Zdenko Časar、Miha Steinbücher、Janez Košmrlj

  DOI：10.1021/jo101050z

  日期：2010.10.1

  The first entry to statins via lactonized side chain is reported, exemplified by the synthesis of rosuvastatin. The key step is Wittig coupling of (2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxotetrahydro-2H-pyran-2-carbaldehyde and phosphonium salt of an appropriately functionalized pyrimidine heterocycle. One-pot deprotection and hydrolysis of the resulting 4-O-TBS rosuvastatin lactone provided rosuvastatin

  据报道，他汀类药物通过内酯化侧链首次进入，以罗苏伐他汀的合成为例。关键步骤是将（2 S，4 R）-4-（叔丁基二甲基甲硅烷氧基）-6-氧四氢-2 H-吡喃-2-甲醛与适当官能化的嘧啶杂环的phospho盐进行Wittig偶联。一锅脱保护和水解所得4- O- TBS罗苏伐他汀内酯以高收率提供罗苏伐他汀。
• Conformational analysis of E/Z-isomeric pairs of rosuvastatin and its lactonized analogues
  作者：Jan Fabris、Damjan Makuc、Zdenko Časar、Janez Plavec

  DOI：10.1016/j.tet.2013.05.020

  日期：2013.7

  Most of the super-statins contain a C=C double bond spacer between the heterocyclic and the chiral dihydroxycarboxylic moieties. The known drugs are E-geometric isomers, whereas very little is known about their Z-isomeric analogues. This study explains the unusual resonance line broadening observed in 1H NMR spectra of Z-isomeric rosuvastatin analogues at room temperature, which originates from dynamic exchange between different conformers. Conformational equilibria and intrinsic preferences of Z-isomeric rosuvastatin analogues provide valuable insight into conformational variability that is important for studying potential interactions within the binding site of the enzyme. (C) 2013 Elsevier Ltd. All rights reserved.