N-(6-chloro-9-((6aR,8R,9R,9aR)-2,2,4,4-tetraisopropyl-9-((trimethylsilyl)oxy)tetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl)-9H-purin-2-yl)acetamide | 1350981-73-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: N-(6-chloro-9-((6aR,8R,9R,9aR)-2,2,4,4-tetraisopropyl-9-((trimethylsilyl)oxy)tetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl)-9H-purin-2-yl)acetamide
• 英文别名: N-[9-[(6aR,8R,9R,9aR)-2,2,4,4-tetra(propan-2-yl)-9-trimethylsilyloxy-6a,8,9,9a-tetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl]-6-chloropurin-2-yl]acetamide
• CAS: 1350981-73-5
• 化学式: C₂₇H₄₈ClN₅O₆Si₃
• 分子量: 658.418
• InChiKey: BCRBNOKLDBHESD-HUBRGWSESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.51
• 重原子数：
  42
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  119
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-(6-chloro-9-((6aR,8R,9R,9aR)-2,2,4,4-tetraisopropyl-9-((trimethylsilyl)oxy)tetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl)-9H-purin-2-yl)acetamide 在 吡啶 、 chromium(VI) oxide 、 aluminum (III) chloride 、 二乙胺基三氟化硫 、 四丁基氟化铵 、 乙酸酐 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 为溶剂， 反应 27.0h， 生成 [4-¹³C]-(2R,3R,4R,5R)-5-(2-acetamido-6-chloro-9H-purin-9-yl)-2-(acetoxymethyl)-4-fluoro-4-trideuteromethyltetrahydrofuran-3-yl acetate
  参考文献：
  名称：

  プリンヌクレオシドの合成

  摘要：

  要解决的问题：提供用于治疗由病毒因素引起的疾病的化合物。解决方案：本发明提供由式（I）或式（II）代表的化合物或其盐，以及它们的合成方法。（其中，R1是苯基或类似物；R2是H或类似物；R3a和R3b分别独立地是H、C1-10烷基或类似物；R4是H、C1-10烷基、C3-10环烷基或类似物；R5是H或类似物；R6是H、CH3或类似物；R7是H、n-烷基、环烷基或类似物；R8是O（较低烷基）、O（较低环烷基）或类似物；R9是NH2基团或类似物。）

  公开号：

  JP2015227337A
• 作为产物：
  描述：

  2-amino-6-chloro-9-[3,5-O-(tetraisopropyldisiloxane-1,3-diyl)-β-D-ribofuranosyl]purine 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 N-(6-chloro-9-((6aR,8R,9R,9aR)-2,2,4,4-tetraisopropyl-9-((trimethylsilyl)oxy)tetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl)-9H-purin-2-yl)acetamide
  参考文献：
  名称：

  Synthesis of Stable Isotope Labeled Analogs of the Anti-Hepatitis C Virus Nucleotide Prodrugs PSI-7977 and PSI-352938

  摘要：

  In order to support bioanalytical LC/MS method development and plasma sample analysis in preclinical and clinical studies of the anti-hepatitis C-virus nucleotides, PSI-7977 and PSI-352938, the corresponding stable isotope labeled forms were prepared. These labeled compounds were prepared by addition reaction of the freshly prepared Grignard reagent (CD3MgI)-C-13 to the corresponding 2'-ketone nucleosides followed by fluorination of the resulting carbinol with DAST. As expected, these 2'-C-(trideuterated-C-13-methyl) nucleotide prodrugs showed similar anti-HCV activity to that of the corresponding unlabeled ones.

  DOI：

  10.1080/15257770.2011.614308

文献信息

• プリンヌクレオシドの合成
  申请人：ギリアド ファーマセット エルエルシー

  公开号：JP2015227337A

  公开（公告）日：2015-12-17

  PROBLEM TO BE SOLVED: To provide compounds useful for treating conditions caused by viral factors.SOLUTION: The present invention provides compounds represented by formula (I) or formula (II) or salts thereof, and methods of synthesizing the same. (R1 is phenyl group or the like; R2 is H or the like; R3a and R3b are each independently H, a C1-10 alkyl group, or the like; R4 is H, a C1-10 alkyl group, a C3-10 cycloalkyl group, or the like; R5 is H or the like; R6 is H, CH3, or the like; R7 is H, an n-alkyl group, a cycloalkyl group, or the like; R8 is O (lower alkyl), O (lower cycloalkyl), or the like; and R9 is an NH2 group or the like.)

  要解决的问题：提供用于治疗由病毒因素引起的疾病的化合物。解决方案：本发明提供由式（I）或式（II）代表的化合物或其盐，以及它们的合成方法。（其中，R1是苯基或类似物；R2是H或类似物；R3a和R3b分别独立地是H、C1-10烷基或类似物；R4是H、C1-10烷基、C3-10环烷基或类似物；R5是H或类似物；R6是H、CH3或类似物；R7是H、n-烷基、环烷基或类似物；R8是O（较低烷基）、O（较低环烷基）或类似物；R9是NH2基团或类似物。）
• Synthesis of Stable Isotope Labeled Analogs of the Anti-Hepatitis C Virus Nucleotide Prodrugs PSI-7977 and PSI-352938
  作者：Byoung-Kwon Chun、Jinfa Du、Hai-Ren Zhang、Wonsuk Chang、Bruce S. Ross、Ying Jiang、Donghui Bao、Christine L. Espiritu、Meg Keilman、Holly M. Micolochick Steuer、Phillip A. Furman、Michael J. Sofia

  DOI：10.1080/15257770.2011.614308

  日期：2011.11

  In order to support bioanalytical LC/MS method development and plasma sample analysis in preclinical and clinical studies of the anti-hepatitis C-virus nucleotides, PSI-7977 and PSI-352938, the corresponding stable isotope labeled forms were prepared. These labeled compounds were prepared by addition reaction of the freshly prepared Grignard reagent (CD3MgI)-C-13 to the corresponding 2'-ketone nucleosides followed by fluorination of the resulting carbinol with DAST. As expected, these 2'-C-(trideuterated-C-13-methyl) nucleotide prodrugs showed similar anti-HCV activity to that of the corresponding unlabeled ones.