(2R,4S)-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-piperazine | 214117-53-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (2R,4S)-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-piperazine
• 英文别名: 1-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine
• CAS: 214117-53-0
• 化学式: C₂₃H₂₅Cl₂N₅O₃
• 分子量: 490.389
• InChiKey: SOLQXQASKIOXJI-REWPJTCUSA-N

物化性质

• 沸点：
  692.0±65.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  73.7
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2R,4S)-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-piperazine 在 palladium on activated charcoal 噻吩 、 吡啶 、 氢气 、 potassium carbonate 、 一水合肼 作用下， 以 1,4-二氧六环 、 甲醇 、 氯仿 、 乙二醇甲醚 、 二甲基亚砜 为溶剂， 反应 6.0h， 生成 伊曲康唑杂质20
  参考文献：
  名称：

  Antimycotic azoles. 7. Synthesis and antifungal properties of a series of novel triazol-3-ones

  摘要：

  A series of novel triazol-3-ones have been synthesized, and their in vitro and in vivo antifungal properties are reported. Compound 68 (itraconazole), which displays a pronounced oral activity against vaginal candidosis in rats and against microsporosis in guinea pigs, has been selected for clinical evaluation.

  DOI：

  10.1021/jm00373a015
• 作为产物：
  描述：

  1-(2,4-二氯l苯基)-2-(1H-1,2,4-噻唑-1-基)-乙酮 在 氢氧化钾 、 三氟甲磺酸 、 sodium hydride 作用下， 以 水 、 N,N-二甲基甲酰胺 、 异丙醇 、 甲苯 为溶剂， 反应 89.0h， 生成 (2R,4S)-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-piperazine
  参考文献：
  名称：

  Total synthesis of (2R,4S,2′S,3′R)-hydroxyitraconazole: implementations of a recycle protocol and a mild and safe phase-transfer reagent for preparation of the key chiral units

  摘要：

  A convergent total synthesis of enantiomerically-pure (2R,4S,2'S,3'R)-hydroxyitraconazole 1b is described. The left dioxolane portion of the molecule was prepared in good yield by the conversion of (S)-10 to the corresponding enantiomerically and diastereomerically-pure acetonide (2R,4R)-3 by a recycle protocol involving diastereoselective crystallization of the tosylate salt, followed by re-equilibration of the mother liquor and crystallization. The right-hand triazolone moeity (2S,3R)-4 was generated by alkyaltion of triazolone 6 with enantiomerically pure cyclic sulfate (4R,5R)-7 under mild and essentially non-hazardous reaction conditions (TDA-1, K2CO3, acetonitrile). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2003.01.001

文献信息

• 一种伊曲康唑衍生物的制备方法
  申请人：梯尔希(南京)药物研发有限公司

  公开号：CN108329304B

  公开（公告）日：2020-12-08

  本发明公开了一种伊曲康唑衍生物的制备方法，本发明以1‑乙酰‑4‑(4‑羟基苯基)哌嗪为原料，通过六步反应，实现伊曲康唑衍生物的合成。本发明提供的制备方法，工艺设计合理，可操作性强，反应条件比较温和，产率高，可实现工业化生产。本发明制备得到的伊曲康唑衍生物，可为伊曲康唑质量、安全性和效能科学评价提供重要依据，并且伊曲康唑衍生物药理活性好，可开发用于治疗各种原因引起的真菌感染的药物，具有重要的应用价值。
• Pd-catalyzed aminations of aryl triazolones: Effective synthesis of hydroxyitraconazole enantiomers
  作者：Gerald J. Tanoury、Chris H. Senanayake、Robert Hett、Amy M. Kuhn、Donald W. Kessler、Stephen A. Wald

  DOI：10.1016/s0040-4039(98)01493-2

  日期：1998.9

  A palladium-catalyzed amination of triazolone 3 by piperazine 2 was used as the key step in an efficient synthesis of highly enantiomerically-pure hydroxyitraconazole isomers. Compound 2 (>99%ee) was prepared by reaction of an achiral phenol precursor with the corresponding dioxolyl tosylate (>99% ee), and 3 was made by alkylation of 6 with 7 (>99%ee). (C) 1998 Elsevier Science Ltd. All rights reserved.
• HEERES, J.;BACKX, L. J. J.;MOSTMANS, J. H.
  作者：HEERES, J.、BACKX, L. J. J.、MOSTMANS, J. H.

  DOI：——

  日期：——
• Antimycotic azoles. 7. Synthesis and antifungal properties of a series of novel triazol-3-ones
  作者：J. Heeres、L. J. J. Backx、J. Van Cutsem

  DOI：10.1021/jm00373a015

  日期：1984.7

  A series of novel triazol-3-ones have been synthesized, and their in vitro and in vivo antifungal properties are reported. Compound 68 (itraconazole), which displays a pronounced oral activity against vaginal candidosis in rats and against microsporosis in guinea pigs, has been selected for clinical evaluation.
• Total synthesis of (2R,4S,2′S,3′R)-hydroxyitraconazole: implementations of a recycle protocol and a mild and safe phase-transfer reagent for preparation of the key chiral units
  作者：Gerald J. Tanoury、Robert Hett、H.Scott Wilkinson、Stephen A. Wald、Chris H. Senanayake

  DOI：10.1016/j.tetasy.2003.01.001

  日期：2003.11

  A convergent total synthesis of enantiomerically-pure (2R,4S,2'S,3'R)-hydroxyitraconazole 1b is described. The left dioxolane portion of the molecule was prepared in good yield by the conversion of (S)-10 to the corresponding enantiomerically and diastereomerically-pure acetonide (2R,4R)-3 by a recycle protocol involving diastereoselective crystallization of the tosylate salt, followed by re-equilibration of the mother liquor and crystallization. The right-hand triazolone moeity (2S,3R)-4 was generated by alkyaltion of triazolone 6 with enantiomerically pure cyclic sulfate (4R,5R)-7 under mild and essentially non-hazardous reaction conditions (TDA-1, K2CO3, acetonitrile). (C) 2003 Elsevier Ltd. All rights reserved.