p-toluenesulfonyloxymethylphosphonic acid | 161760-09-4

• 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 - 苯类化合物 - 苯和取代衍生物
• 英文名称: p-toluenesulfonyloxymethylphosphonic acid
• 英文别名: ((tosyloxy)methyl)phosphonic acid；Tosyloxymethylphosphonic acid；(4-methylphenyl)sulfonyloxymethylphosphonic acid
• CAS: 161760-09-4
• 化学式: C₈H₁₁O₆PS
• 分子量: 266.212
• InChiKey: LVOASXNJWPROPP-UHFFFAOYSA-N

物化性质

• 沸点：
  502.6±52.0 °C(Predicted)
• 密度：
  1.538±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  p-toluenesulfonyloxymethylphosphonic acid 在 吡啶 、 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 生成 [bis(3-(hexadecyloxy)propoxy)phosphoryl]methyl tosylate
  参考文献：
  名称：

  Synthesis and antiviral activities of hexadecyloxypropyl prodrugs of acyclic nucleoside phosphonates containing guanine or hypoxanthine and a (S)-HPMP or PEE acyclic moiety

  摘要：

  Hexadecyloxypropyl esters of acyclic nucleoside phosphonates containing guanine (G) or hypoxanthine (Hx) and a (S)-[3-hydroxy-2-(phosphonomethoxy)propyl] [(S)-HPMP] or 2-(2-phosphonoethoxy)ethyl (PEE) acyclic moiety have been prepared. The activity of the prodrugs was evaluated in vitro against different virus families. Whereas ester derivatives of PEEHx and (S)-HPMPHx were antivirally inactive, monoesters of PEEG, and mono- and diesters of (S)-HPMPG showed pronounced antiviral activity against vaccinia virus and/or herpesviruses. Monoesters of (S)-HPMPG emerged as the most potent and selective derivatives against these DNA viruses. None of the compounds were inhibitory against RNA viruses and retroviruses. Crown Copyright (C) 2012 Published by Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.07.027
• 作为产物：
  描述：

  对甲苯磺酰氧甲基膦酸二乙酯 在 甲醇 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 25.0h， 生成 p-toluenesulfonyloxymethylphosphonic acid
  参考文献：
  名称：

  Rovafovir Etalafenamide的合成（第三部分）：合成膦酰胺盐片段的合成过程的演变

  摘要：

  膦酰氨基甲酸酯1是rovafovir etalafenamide组装过程中的关键片段，该药物是Gilead Sciences研发的用于治疗HIV感染的新型核苷酸逆转录酶抑制剂。依靠模拟移动床（SMB）色谱法分离磷非对映异构体的早期生产路线可大规模生产1批。但是，考虑到与SMB相关的高生产成本，长交货期和高工艺质量强度（PMI），开发替代合成条件变得合乎需要。本文描述了几种改善这些因素的策略，包括差向异构化和不需要的（R）-磷非对映异构体，设计立体选择性方法以在磷处建立所需的（S）-构型，并鉴定条件或衍生物以允许选择性结晶。最终，开发了第二代至1的途径并进行了规模论证。新路线通过选择性结晶实现了磷非对映异构体的分离，不需要SMB，并提供了更低的PMI，成本和交货时间。

  DOI：

  10.1021/acs.oprd.0c00428

文献信息

• Novel Phosphinic Acid-Containing Thyromimetics
  申请人：Erion Mark D.

  公开号：US20090028925A1

  公开（公告）日：2009-01-29

  The present invention relates to compounds of phosphonic acid-containing T3 mimetics and monoesters thereof, stereoisomers, pharmaceutically acceptable salts, co-crystals, and prodrugs thereof and pharmaceutically acceptable salts and co-crystals of the prodrugs, as well as their preparation and uses for preventing and/or treating metabolic diseases such as obesity, NASH, hypercholesterolemia and hyperlipidemia, as well as associated conditions such as atherosclerosis, coronary heart disease, impaired glucose tolerance, metabolic syndrome x and diabetes.

  本发明涉及含有磷酸基T3拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟
• Novel compounds and methods for therapy
  申请人：INSTITUTE OF ORGANIC CHEMISTRY AND BIOCHEMISTRY ACADEMY OF SCIENCES

  公开号：US20030109499A1

  公开（公告）日：2003-06-12

  Novel compounds are provided having formula (I) 1 where R 1 , R 2 , R 3 , R 4 , Z, X and * are defined herein. Also provided are antiviral methods for use and processes for synthesis of the compounds of formula (I).

  提供具有以下化学式（I）的新化合物： 其中 R 1 ，R 2 ，R 3 ，R 4 ，Z，X和*在此处定义。还提供了用于抗病毒方法和合成化合物（I）的过程。
• Phosphonate Ester Derivatives and Methods of Synthesis Thereof
  申请人：Ware Roy W.

  公开号：US20120058976A1

  公开（公告）日：2012-03-08

  The disclosure describes methods of synthesis of phosphonate ester derivatives. Preferred methods according to the disclosure allow for large-scale preparation of phosphonate ester compounds having high purity. In some embodiments, preferred methods according to the disclosure also allow for the preparation of phosphonate ester derivatives without the use of chromatographic purification methods and in better yield than previously used methods for preparing such compounds. Also disclosed are morphic forms of phosphonate ester derivatives.

  该披露描述了合成膦酸酯衍生物的方法。根据该披露的首选方法允许大规模制备高纯度的膦酸酯化合物。在一些实施例中，根据该披露的首选方法还允许在比以往用于制备这类化合物的方法更好的产率下制备膦酸酯衍生物，而无需使用色谱纯化方法。还披露了膦酸酯衍生物的形态形式。
• An improved process for the preparation of Tenofovir disoproxil and pharmaceutically acceptable salts thereof
  申请人：Zentiva, k.s.

  公开号：EP2860185A1

  公开（公告）日：2015-04-15

  An improved process for the preparation of Tenofovir disoproxil and pharmaceutically acceptable salts thereof, comprising following steps: a) alkylation of adenine with (R)-4-methyl-1,3-dioxolan-2-one and isolation of (R)-1-(6-amino-9H-purin-9-yl)propan-2-ol; b) alkylation of (R)-1-(6-amino-9H-purin-9-yl) propan-2-ol with a dialkyl p-toluenesulphonyloxymethylphosphonate or dialkyl halomethylphosphonate to give dialkylester of (R)-9-[2-(phosphonomethoxy)propyl]adenine; c) preparation of (R)-9-[2-(phosphonomethoxy)propyl]adenine ((R)-PMPA; Tenofovir) by dealkylation of the phosphonate moiety with a mineral acid under microwave irradiation; d) preparation of Tenofovir disoproxil; e) preparation of the fumarate salt or other pharmaceutically acceptable salt of Tenofovir disoproxil.

  一种改进的Tenofovir disoproxil及其药用盐的制备方法，包括以下步骤：a) 使用(R)-4-甲基-1,3-二氧杂环戊酮烷基化腺嘌呤并分离(R)-1-(6-氨基-9H-嘌呤-9-基)丙醇；b) 使用二烷基对甲苯磺酰氧甲基膦酸酯或二烷基卤代甲基膦酸酯对(R)-1-(6-氨基-9H-嘌呤-9-基)丙醇进行烷基化，得到(R)-9-[2-(磷酸甲氧基)丙基]腺嘌呤的二烷基酯；c) 通过微波辐射下使用矿酸去烷基化磷酸酯部分，制备(R)-9-[2-(磷酸甲氧基)丙基]腺嘌呤((R)-PMPA; Tenofovir)；d) 制备Tenofovir disoproxil；e) 制备Tenofovir disoproxil的富马酸盐或其他药用可接受的盐。
• [EN] ACYCLIC ANTIVIRALS<br/>[FR] ANTIVIRAUX ACYCLIQUES
  申请人：ALIOS BIOPHARMA INC

  公开号：WO2017156262A1

  公开（公告）日：2017-09-14

  Disclosed herein are nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a HBV and/or HDV and/or HIV infection with one or more nucleotide analogs

  本文揭示了核苷酸类似物，合成核苷酸类似物的方法以及使用一个或多个核苷酸类似物治疗HBV、HDV和/或HIV感染等疾病和/或状况的方法。