4-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-2-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-3(2H,4H)-1,2,4-triazolone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-2-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-3(2H,4H)-1,2,4-triazolone
• 英文别名: 2-[4-(1,1,2,2-Tetrafluoroethoxy)phenyl]-4-[(1R,2R)-1-methyl-2-hydroxy-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propyl]-2H-1,2,4-triazol-3(4H)-one；4-[(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1,2,4-triazol-1-yl)butan-2-yl]-2-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-1,2,4-triazol-3-one
• 化学式: C₂₂H₁₈F₆N₆O₃
• 分子量: 528.414
• InChiKey: RAKMFLDDMWCFEA-LRTDBIEQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  96.1
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  2-((1R)-1-(2-(2,4-二氟苯基)氧基-2-基)乙氧基)四氢-2H-吡喃 在 sodium hydroxide 、 sodium methylate 、 4-甲基苯磺酸吡啶 、 sodium hydride 、 三乙胺 、 N,N-二异丙基乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.67h， 生成 4-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-2-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-3(2H,4H)-1,2,4-triazolone
  参考文献：
  名称：

  Optically Active Antifungal Azoles. VI. Synthesis and Antifungal Activity of N-((1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl)-N'-(4-substituted phenyl)-3(2H,4H)-1,2,4-triazolones and 5(1H,4H)-tetrazolones.

  摘要：

  通过(1S)-1-[(2R)-2-(2,4-二氟苯基)-2-环氧乙烷基]乙醇的三氟甲磺酸酯衍生物与一种吖唑酮阴离子经SN2取代反应及随后与1H-1,2,4-三氮唑的开环反应制备了一系列具有光学活性的新型抗真菌唑类化合物，N-[(1R,2R)-2-(2,4-二氟苯基)-2-羟基-1-甲基-3-(1H-1,2,4-三唑-1-基)丙基]-N'-(4-取代苯基)-3(2H,4H)-1,2,4-三唑酮(1,2)和5(1H,4H)-四唑酮(3)。手性环氧乙烷乙醇13是以立体控制方式由甲基(R)-乳酸制得。所制得的吖唑酮1-3在体外及体内均展现出强大的抗真菌活性。

  DOI：

  10.1248/cpb.44.314

文献信息

• Optically active azole derivatives, their production and use
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：EP0659751A1

  公开（公告）日：1995-06-28

  A process for preparing a compound of the formula (IV) or a salt thereof, , wherein R¹ is an optionally substituted aliphatic or aromatic hydrocarbon residue or an optionally substituted aromatic heterocyclic group, one of Y and Z is a nitrogen atom and the other is a methine group which may be optionally substituted with a lower alkyl group, Ar is a halogenated phenyl group, and (R) shows that the carbon atom marked with (R) has (R)-configuration, in a short period, by simple processes and with high yield and purity; and an azole compound of the formula (IV'), , wherein Ar' is a monofluorophenyl group, and the other symbols have the same meanings as above, or a salt thereof, which are useful for an antifungal therapeutic agent.

  一种制备式（IV）化合物或其盐的方法，其中R¹是可选取的取代脂肪族或芳香烃基残基或可选取的取代芳香杂环基团，Y和Z中的一个是氮原子，另一个是可能被低烷基取代的甲基基团，Ar是卤代苯基团，（R）表示标有（R）的碳原子具有（R）-构型，通过简单的过程，在短时间内高产量和高纯度地制备出所述化合物；以及式（IV'）的唑类化合物或其盐，其中Ar'是单氟苯基团，其他符号具有与上述相同的含义，这些化合物对于抗真菌治疗剂是有用的。
• Production of optically active triazole compounds and their intermediates
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：EP0687672A2

  公开（公告）日：1995-12-20

  A compound of the formula (V): wherein Ar' is a halogenated phenyl group, R is a hydrocarbon residue having a functional group at the α-carbon, R3' is an optionally substituted aliphatic or aromatic hydrocarbon residue or an optionally substituted aromatic heterocyclic group, Y and Z are, the same or different, a nitrogen atom or a methine group optionally substituted with a lower alkyl group, and (R) and (S) represent configurations, which is an optically active intermediate for production of optically active triazole compounds (I): wherein the symbols have the same meanings as defined above, and methods of preparing the compounds (V) and (I). The compound (25) -2'-fluoro-2-hydroxy-propiophenone which is an intermediate for production of compounds (V). Furthermore a compound of the formula (Va'): wherein Ar' is a halogenated phenyl group, R is a hydrocarbon residue having a functional group at the α-carbon, R3' is an optionally substituted aliphatic or aromatic hydrocarbon residue or an optionally substituted aromatic heterocyclic group, and (R) and (S) represent configurations, which is an intermediate for preparing a compound of formula (I'): and a method of preparing a compound of the formula (Va').

  式 (V) 的化合物： 其中 Ar'是卤代苯基，R 是在α-碳上具有官能团的烃残基，R3'是任选取代的脂肪族或芳香族烃残基或任选取代的芳香族杂环基团，Y 和 Z 是相同或不同的氮原子或任选被低级烷基取代的甲基，(R)和(S)代表构型，它是生产光学活性三唑化合物(I)的光学活性中间体： 其中符号的含义与上述定义相同，以及化合物（V）和（I）的制备方法。化合物（25）-2'-氟-2-羟基苯丙酮，它是生产化合物（V）的中间体。此外还有式（Va'）化合物： 其中 Ar'是卤代苯基，R 是在α-碳处具有官能团的烃残基，R3'是任选取代的脂肪族或芳香族烃残基或任选取代的芳香族杂环基团，且 (R) 和 (S) 代表构型，该化合物是制备式 (I') 化合物的中间体： 以及一种制备式（Va'）化合物的方法。
• Process for the preparation of optically active triazole derivatives and their imidazolidin-2-one intermediates
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：EP1033367A2

  公开（公告）日：2000-09-06

  A compound of the formula (Va') wherein    Ar' is a halogenated phenyl group, R is a hydrocarbon residue having, at the α-carbon, a functional group selected from a silyl group, a double bond and an optionally activated hydroxyl group,    R3' is an optionally substituted aliphatic or aromatic hydrocarbon residue or an optionally substituted aromatic heterocyclic group, and (R) and (S) represent configurations, which is an optically active intermediate for production of optically active triazole compounds (I'): wherein the symbols have the same meanings as defined above, and methods of preparing the compounds (Va') and (I').

  式（Va'）化合物 其中 Ar' 是卤代苯基，R 是在α-碳上具有选自硅烷基、双键和任选活化羟基的官能团的烃残基、 R3'是任选取代的脂肪族或芳香族烃残基或任选取代的芳香族杂环基团，(R)和(S)代表构型，是生产光学活性三唑化合物（I'）的光学活性中间体： 其中 符号的含义与上述定义相同，以及化合物（Va'）和（I'）的制备方法。
• Azole compounds, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0567982B1

  公开（公告）日：1998-07-01
• US5371101A
  申请人：——

  公开号：US5371101A

  公开（公告）日：1994-12-06