6N-羟甲基替诺福韦二吡呋酯 | 1244022-53-4

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 6N-羟甲基替诺福韦二吡呋酯
• 中文别名: 6N-羟基甲基替诺福韦酯；6N-羟基甲基替诺福韦二吡呋酯；替诺福韦酯杂质XIII
• 英文名称: 2,4,6,8-Tetraoxa-5-phosphanonanedioic acid, 5-[[(1R)-2-[6-[(hydroxymethyl)amino]-9H-purin-9-yl]-1-methylethoxy]methyl]-, 1,9-bis(1-methylethyl) ester, 5-oxide
• 英文别名: [[(2R)-1-[6-(hydroxymethylamino)purin-9-yl]propan-2-yl]oxymethyl-(propan-2-yloxycarbonyloxymethoxy)phosphoryl]oxymethyl propan-2-yl carbonate
• CAS: 1244022-53-4
• 化学式: C₂₀H₃₂N₅O₁₁P
• 分子量: 549.475
• InChiKey: OCSNDZVWYFILJW-OAHLLOKOSA-N

物化性质

• 沸点：
  687.9±65.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于二氯甲烷、乙酸乙酯

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  37
• 可旋转键数：
  19
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  192
• 氢给体数：
  2
• 氢受体数：
  15

安全信息

• 储存条件：
  室温且干燥

反应信息

• 作为产物：
  描述：

  腺嘌呤 在 三甲基氯硅烷 、 magnesium 2-methylpropan-2-olate 、 三乙胺 、 sodium bromide 、 sodium hydroxide 作用下， 以 N-甲基吡咯烷酮 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 替诺福韦杂质W 、 6N-羟甲基替诺福韦二吡呋酯
  参考文献：
  名称：

  Process Improvements for the Manufacture of Tenofovir Disoproxil Fumarate at Commercial Scale

  摘要：

  The three-step manufacturing process used in the synthesis of tenofovir disoproxil fumarate (1) was studied and optimized, leading to a more productive and robust process. The yield was improved from about 13% overall to 24%. Key process improvements identified included implementation of a telescoped process for the second stage that obviated the need for an extraction and solvent exchange, and significant optimization of the final reaction, including the beneficial effect of adding a quaternary ammonium salt to the alkylation reaction and development of a nonaqueous process for removal of NMP and triethylamine from the product mixture to decrease the level of decomposition of product during the isolation.

  DOI：

  10.1021/op1001337

文献信息

• 一种富马酸替诺福韦酯杂质的制备工艺
  申请人：深圳菲斯生物科技有限公司

  公开号：CN106699813A

  公开（公告）日：2017-05-24

  一种富马酸替诺福韦酯杂质的制备工艺。本发明公开了2个富马酸替诺福韦酯杂质的合成方法，两个杂质的结构分别为式I化合物和式II化合物，以富马酸替诺福韦酯为原料，在反应溶剂中与多聚甲醛发生反应而得到，式I和式II均可作为富马酸替诺福韦酯的有关物质检测的对照品，有助于富马酸替诺福韦酯质量控制以及制剂纯度的控制。
• Process Improvements for the Manufacture of Tenofovir Disoproxil Fumarate at Commercial Scale
  作者：David H. Brown Ripin、David S. Teager、Joseph Fortunak、Shaik Mahaboob Basha、Nylea Bivins、Christopher N. Boddy、Stephen Byrn、Kelly K. Catlin、Stephen R. Houghton、S. Tirumala Jagadeesh、K. Anesh Kumar、Jack Melton、Shaik Muneer、L. Nagaprasada Rao、R. Venkateswara Rao、Puma Chandra Ray、Nardla Gopal Reddy、Ravi Mallikarjuna Reddy、K. Chandra Shekar、Tricia Silverton、Daniel T. Smith、Rodger W. Stringham、Gottumukkala V. Subbaraju、Frajovon Talley、Adrian Williams

  DOI：10.1021/op1001337

  日期：2010.9.17

  The three-step manufacturing process used in the synthesis of tenofovir disoproxil fumarate (1) was studied and optimized, leading to a more productive and robust process. The yield was improved from about 13% overall to 24%. Key process improvements identified included implementation of a telescoped process for the second stage that obviated the need for an extraction and solvent exchange, and significant optimization of the final reaction, including the beneficial effect of adding a quaternary ammonium salt to the alkylation reaction and development of a nonaqueous process for removal of NMP and triethylamine from the product mixture to decrease the level of decomposition of product during the isolation.