(2S,3S)-3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1,2,4-triazol-1-yl)butan-2-ol

• 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: (2S,3S)-3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1,2,4-triazol-1-yl)butan-2-ol
• 化学式: C₁₆H₁₃ClF₃N₅O
• 分子量: 383.76
• InChiKey: BQDLXFABVRRDFU-FVMDXXJSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  76.7
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  氟代丙酰基乙酸乙酯 在 甲醇 、 sodium methylate 、 lithium diisopropyl amide 、 三氯氧磷 作用下， 以 四氢呋喃 为溶剂， 生成 (2S,3S)-3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1,2,4-triazol-1-yl)butan-2-ol
  参考文献：
  名称：

  Novel antifungal 2-aryl-1-(1H-1,2,4-triazol-1-yl)butan-2-ol derivatives with high activity against Aspergillus fumigatus

  摘要：

  Replacement of one triazole ring of fluconazole with 4-pyridinyl leads to an increase in activity against Aspergillus fumigatus. Introduction of an alpha-methyl group has a marked additional beneficial effect. Investigation of pyridinyl and pyrimidinyl analogues resulted in the identification of 30 (UK-109,496, voriconazole) which has excellent potency against a broad range of fungal pathogens including A. fumigatus and Candida krusei. Copyright (C) 1996 Elsevier Science Ltd.

  DOI：

  10.1016/0960-894x(96)00363-0

文献信息

• Preparation of triazoles by organometallic addition to ketones and intermediates therefor
  申请人：Pfizer, Inc.

  公开号：US06586594B1

  公开（公告）日：2003-07-01

  A process for the preparation of a compound of the formula: or an acid addition or base salt thereof, wherein R is phenyl optionally substituted by 1 to 3 substituents each independently selected from halo and trifluoromethyl; R1 is C1-C6 alkyl; and “Het” is pyrimidinyl optionally substituted by 1 to 3 substituents each independently selected from C1-C4 alkyl, C1-C4 alkoxy, halo, oxo, benzyl and benzyloxy, comprising reacting a compound of the formula: with a compound of the formula wherein X is chloro, bromo or iodo, the reaction taking place in the presence of zinc; at least one of iodine or a Lewis acid; and an aprotic organic solvent: optionally further reacting the resulting compound with an acid or base to form the corresponding acid addition or base salt thereof.

  该方法用于制备以下化合物：或其酸加合物或碱盐，其中R是苯基，可以选择地被1至3个取代基取代，每个取代基独立地选自卤素和三氟甲基；R1是C1-C6烷基；“Het”是嘧啶基，可以选择地被1至3个取代基取代，每个取代基独立地选自C1-C4烷基、C1-C4烷氧基、卤素、氧代基、苄基和苄氧基，包括将以下化合物与以下化合物反应：其中X是氯、溴或碘，在锌的存在下进行反应；至少使用碘或路易斯酸；和无水有机溶剂：可选择进一步将所得化合物与酸或碱反应，形成相应的酸加合物或碱盐。
• IMPROVED PROCESS FOR THE PREPARATION OF 2R, 3S-2-(2,4-DIFLUOROPHENYL)-3-(5-FLUOROPYRIMIDIN-4-YL)-1-(1H-1,2,4-TRIAZOL-1-YL) BUTAN-2-OL (VORICONAZOLE)
  申请人：MSN Laboratories Limited

  公开号：EP1899327A1

  公开（公告）日：2008-03-19
• US8039619B2
  申请人：——

  公开号：US8039619B2

  公开（公告）日：2011-10-18
• [EN] IMPROVED PROCESS FOR THE PREPARATION OF 2R, 3S-2-(2,4-DIFLUOROPHENYL)-3-(5-FLUOROPYRIMIDIN-4-YL)-1-(1H-1,2,4-TRIAZOL-1-YL) BUTAN-2-OL (VORICONAZOLE)<br/>[FR] PROCEDE AMELIORE DESTINE A LA PREPARATION DE 2R, 3S-2-(2,4-DIFLUOROPHENYL)-3-(5-FLUOROPYRIMIDIN-4-YL)-1-(1H-1,2,4-TRIAZOL-1-YL) BUTAN-2-OL (VORICONAZOLE)
  申请人：MSN LAB LTD

  公开号：WO2007013096A1

  公开（公告）日：2007-02-01

  [EN] Improved process for the preparation of 2r, 3s-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1h-1,2,4-triazol-1-yl) butan-2-ol (voriconazole).
  [FR] Procedé amelioré destiné a la preparation de 2r, 3s-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1h-1,2,4-triazol-1-yl) butan-2-ol (voriconazole).
• Novel antifungal 2-aryl-1-(1H-1,2,4-triazol-1-yl)butan-2-ol derivatives with high activity against Aspergillus fumigatus
  作者：Roger P. Dickinson、Andrew S. Bell、Christopher A. Hitchcock、Subramaniyan Narayanaswami、Stephen J. Ray、Kenneth Richardson、Peter F. Troke

  DOI：10.1016/0960-894x(96)00363-0

  日期：1996.8

  Replacement of one triazole ring of fluconazole with 4-pyridinyl leads to an increase in activity against Aspergillus fumigatus. Introduction of an alpha-methyl group has a marked additional beneficial effect. Investigation of pyridinyl and pyrimidinyl analogues resulted in the identification of 30 (UK-109,496, voriconazole) which has excellent potency against a broad range of fungal pathogens including A. fumigatus and Candida krusei. Copyright (C) 1996 Elsevier Science Ltd.