[3-[(4-benzoylpiperazin-1-yl)(oxo)acetyl]-4-fluoro-7-(1H-1,2,3-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-1-yl]methyl dihydrogen phosphate, L-lysine salt

• 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: [3-[(4-benzoylpiperazin-1-yl)(oxo)acetyl]-4-fluoro-7-(1H-1,2,3-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-1-yl]methyl dihydrogen phosphate, L-lysine salt
• 英文别名: [3-[2-(4-benzoylpiperazin-1-yl)-2-oxoacetyl]-4-fluoro-7-(triazol-1-yl)pyrrolo[2,3-c]pyridin-1-yl]methyl dihydrogen phosphate;(2S)-2,6-diaminohexanoic acid
• 化学式: C₆H₁₄N₂O₂*C₂₃H₂₁FN₇O₇P
• 分子量: 703.624
• InChiKey: NZRDEQNEQBSULF-ZSCHJXSPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.52
• 重原子数：
  49
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  262
• 氢给体数：
  5
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  1-(4-benzoyl-piperazin-1-yl)-2-(4-fluoro-7-[1,2,3]triazol-1-yl-1H-pyrrolo[2,3-c]pyridin-3-yl)-ethane-1,2-dione 在 水 、 caesium carbonate 、 potassium iodide 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 32.0h， 生成 [3-[(4-benzoylpiperazin-1-yl)(oxo)acetyl]-4-fluoro-7-(1H-1,2,3-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-1-yl]methyl dihydrogen phosphate, L-lysine salt
  参考文献：
  名称：

  Preparation of Phosphonooxymethyl Prodrugs of HIV-1 Attachment Inhibitors

  摘要：

  A practical and scalable synthesis of phosphonooxymethyl prodrugs of HIV-1 attachment inhibitors is described. Starting from azaindoles 1 and 2, this two-step sequence features an efficient alkylation using chloromethyl phosphate 5 and an exceptionally mild deprotection for tert-butyl phosphates. After a salt formation, the API is formed in 82% and 70% overall yield for 3a and 4a, respectively. This chemistry was used to prepare multikilogram quantities of API.

  DOI：

  10.1021/op400225q

文献信息

• Prodrugs of piperazine and substituted piperidine antiviral agents
  申请人：Ueda Yasutsugu

  公开号：US20050209246A1

  公开（公告）日：2005-09-22

  This invention provides for prodrug Compounds I, pharmaceutical compositions thereof, and their use in treating HIV infection. wherein: X is C or N with the proviso that when X is N, R 1 does not exist; W is C or N with the proviso that when W is N, R 2 does not exist; V is C; E is hydrogen or a pharmaceutically acceptable salt thereof; and Y is selected from the group consisting of Also, this invention provides for intermediate Compounds II useful in making prodrug Compounds I. wherein: L and M are independently selected from the group consisting of C 1 -C 6 alkyl, phenyl, benzyl, trialkylsilyl, -2,2,2-trichloroethoxy and 2-trimethylsilylethoxy.

  这项发明提供了前药化合物I，其药物组成物以及它们在治疗HIV感染中的用途。 其中： X为C或N，但当X为N时，R1不存在； W为C或N，但当W为N时，R2不存在；V为C；E为氢或其药用可接受盐；以及 Y从以下组中选择： 此外，这项发明提供了制备前药化合物I的有用中间体化合物II。 其中： L和M独立地选自C1-C6烷基，苯基，苯甲基，三烷基硅基，-2,2,2-三氯乙氧基和2-三甲基硅基乙氧基的组。
• Preparation of Phosphonooxymethyl Prodrugs of HIV-1 Attachment Inhibitors
  作者：David K. Leahy、Shawn K. Pack

  DOI：10.1021/op400225q

  日期：2013.11.15

  A practical and scalable synthesis of phosphonooxymethyl prodrugs of HIV-1 attachment inhibitors is described. Starting from azaindoles 1 and 2, this two-step sequence features an efficient alkylation using chloromethyl phosphate 5 and an exceptionally mild deprotection for tert-butyl phosphates. After a salt formation, the API is formed in 82% and 70% overall yield for 3a and 4a, respectively. This chemistry was used to prepare multikilogram quantities of API.