2,4-dihydro-4-(4-bromophenyl)-2-[(2S,3R)-(3-hydroxy-2-butyl)]-3H-1,2,4-triazol-3-one | 648416-96-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2,4-dihydro-4-(4-bromophenyl)-2-[(2S,3R)-(3-hydroxy-2-butyl)]-3H-1,2,4-triazol-3-one
• 英文别名: 4-(4-bromophenyl)-2-[(2S,3R)-3-hydroxybutan-2-yl]-1,2,4-triazol-3-one
• CAS: 648416-96-0
• 化学式: C₁₂H₁₄BrN₃O₂
• 分子量: 312.166
• InChiKey: OICQLMKEPJEPOD-DTWKUNHWSA-N

物化性质

• 沸点：
  408.5±55.0 °C(Predicted)
• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  56.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,4-dihydro-4-(4-bromophenyl)-2-[(2S,3R)-(3-hydroxy-2-butyl)]-3H-1,2,4-triazol-3-one 在 咪唑 、 tris-(dibenzylideneacetone)dipalladium(0) 、 (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl 、 sodium t-butanolate 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 51.0h， 生成 (2R,4S)-4-[4-[4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]phenyl]-2,4-dihydro-2-[(2S,3R)-3-[(1,1-dimethylethyl)dimethylsiloxy-2-butyl]]-3H-1,2,4-triazol-3-one
  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
• 作为产物：
  描述：

  4-溴异氰酸苯酯 在 三(3,6-二氧杂庚基)胺 、 potassium carbonate 作用下， 以 乙腈 、 正丁醇 为溶剂， 反应 19.75h， 生成 2,4-dihydro-4-(4-bromophenyl)-2-[(2S,3R)-(3-hydroxy-2-butyl)]-3H-1,2,4-triazol-3-one
  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

• 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.