1-(4-fluorophenyl)-1,4-hexanedione | 123184-01-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-fluorophenyl)-1,4-hexanedione
• 英文别名: 1-(4-Fluorophenyl)1,4-hexanedione；1-(4-fluorophenyl)hexane-1,4-dione
• CAS: 123184-01-0
• 化学式: C₁₂H₁₃FO₂
• 分子量: 208.232
• InChiKey: FDRNMBRIMTVQQT-UHFFFAOYSA-N

物化性质

• 熔点：
  47 °C(Solvent: Cyclohexane)
• 沸点：
  331.1±22.0 °C(predicted)
• 密度：
  1.105±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-fluorophenyl)-1,4-hexanedione 、 苯胺 在 对甲苯磺酸 作用下， 反应 0.5h， 生成 2-Ethyl-5-(4-fluorophenyl)-1-phenylpyrrole
  参考文献：
  名称：

  1,5-Diaryl-2-ethyl pyrrole derivatives as antimycobacterial agents: Design, synthesis, and microbiological evaluation

  摘要：

  During the search of novel antitubercular drugs related to BM 212, new diarylpyrroles were designed and synthesized on the basis of a structure-activity relationship analysis of many pyrroles previously described by us. Among them, 1-(4-fluorophenyl)-2-ethyl-3-(thiomorpholin-4-yl)methyl-5-(4-methylphenyl)-1H-pyrrole (2b) proved to be particularly active, with a minimum inhibitory concentration (MIC, expressed as mu g/mL) and a protection index (PI) better than or comparable to those of reference compounds. Also the remaining compounds were very active, although their MIC and PI were in general lower than those of their parent 2-methyl analogues. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.06.005
• 作为产物：
  描述：

  1-戊烯-3-酮 、 对氟苯甲醛 在 3-乙基-5-(2-羟乙基)-4-甲基噻唑溴化物 、 三乙胺 、 盐酸 作用下， 以 水 为溶剂， 反应 0.25h， 生成 1-(4-fluorophenyl)-1,4-hexanedione
  参考文献：
  名称：

  1,5-Diaryl-2-ethyl pyrrole derivatives as antimycobacterial agents: Design, synthesis, and microbiological evaluation

  摘要：

  During the search of novel antitubercular drugs related to BM 212, new diarylpyrroles were designed and synthesized on the basis of a structure-activity relationship analysis of many pyrroles previously described by us. Among them, 1-(4-fluorophenyl)-2-ethyl-3-(thiomorpholin-4-yl)methyl-5-(4-methylphenyl)-1H-pyrrole (2b) proved to be particularly active, with a minimum inhibitory concentration (MIC, expressed as mu g/mL) and a protection index (PI) better than or comparable to those of reference compounds. Also the remaining compounds were very active, although their MIC and PI were in general lower than those of their parent 2-methyl analogues. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.06.005

文献信息

• Process for trans-6-(2-(substituted-pyrrol-1-yl)alkyl)pryan-2-one
  申请人：Warner-Lambert Company

  公开号：US05003080A1

  公开（公告）日：1991-03-26

  An improved process for the preparation of trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-ones by a novel synthesis is described where 1,6-heptadien-4-ol is converted in eight operations to the desired products, as well as an improved process for the preparation of (2R-trans) and trans-(.+-.)-5-(4-fluorophenyl)-2-(1-methylethyl)-N-4-diphenyl-1-[2-tetrah ydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide by a novel synthesis where 4-methyl-3-oxo-N-phenylpentanamide is converted in eight operations to the desired product or alternatively 4-fluoro-.alpha.-[2-methyl-1-oxopropyl]-.gamma.-oxo-N,.beta.-diphenylbenze nebutaneamide is converted in one step to the desired product, and additionally, a process for preparing (2R-trans)-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetrahy dro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide from (R)-4-cyano-3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]butanoic acid, as well as other valuable intermediates used in the processes.

  本文描述了一种改进的方法，通过新型合成将1,6-庚二烯-4-醇转化为所需产物，以制备转-6-[2-(取代吡咯-1-基)烷基]吡喃-2-酮，共进行了八次操作。此外，还描述了一种改进的方法，通过新型合成将4-甲基-3-氧代-N-苯基戊酰胺转化为所需产物，或者通过一步反应将4-氟-α-[2-甲基-1-氧代丙基]-γ-氧代-N，β-二苯基苯基丁酰胺转化为所需产物，以制备(2R-转)和转-(+/-)-5-(4-氟苯基)-2-(1-甲基乙基)-N-4-二苯基-1-[2-四氢-4-羟基-6-氧代-2H-吡喃-2-基)乙基]-1H-吡咯-3-羧酰胺，以及从(R)-4-氰基-3-[[(1,1-二甲基乙基)二甲基硅氧基]丁酸制备(2R-转)-5-(4-氟苯基)-2-(1-甲基乙基)-N,4-二苯基-1-[2-(四氢-4-羟基-6-氧代-2H-吡喃-2-基)乙基]-1H-吡咯-3-羧酰胺，以及用于该过程的其他有价值的中间体。
• Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one
  申请人：Warner-Lambert Company

  公开号：US05149837A1

  公开（公告）日：1992-09-22

  An improved process for the preparation of trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-ones by a novel synthesis is described where 1,6-heptadien-4-ol is converted in eight operations to the desired products, as well as an improved process for the preparation of (2R-trans) and trans-(.+-.)-5-(4-fluoro-phenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetr ahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide by a novel synthesis where 4-methyl-3-oxo-N-phenylpentanamide is converted in eight operations to the desired product or alternatively 4-fluoro-.alpha.-[2-methyl-1-oxopropyl]-.gamma.-oxo-N,.beta.-diphenylbenze nebutaneamide is converted in one step to the desired product, and additionally, a process for preparing (2R-trans)-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetrahy dro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide from (R)-4-cyano-3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]butanoic acid, as well as other valuable intermediates used in the processes.

  本文介绍了一种改进的方法，通过新的合成方法将1,6-庚二烯-4-醇转化为所需产物，制备了转-6-[2-(取代吡咯-1-基)烷基]吡喃-2-酮，共进行了八个步骤。此外，还介绍了一种改进的方法，通过新的合成方法将4-甲基-3-氧代-N-苯基戊酰胺转化为所需产物，或者通过一步将4-氟-α-[2-甲基-1-氧代丙基]-γ-氧代-N，β-二苯基苯丁酰胺转化为所需产物，制备了(2R-转)和转-(.+-.)-5-(4-氟苯基)-2-(1-甲基乙基)-N,4-二苯基-1-[2-(四氢-4-羟基-6-氧代-2H-吡喃-2-基)乙基]-1H-吡咯-3-羧酰胺。此外，还介绍了一种从(R)-4-氰基-3-[[(1,1-二甲基乙基)二甲基硅氧基]丁酸制备(2R-转)-5-(4-氟苯基)-2-(1-甲基乙基)-N,4-二苯基-1-[2-(四氢-4-羟基-6-氧代-2H-吡喃-2-基)乙基]-1H-吡咯-3-羧酰胺的方法，以及用于该过程的其他有价值的中间体。
• Process for trans-6-[12-(substituted-pyrrol-1-yl)alkyl]pyran-2-one
  申请人：Warner-Lambert Co.

  公开号：US05216174A1

  公开（公告）日：1993-06-01

  An improved process for the preparation of trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-ones by a novel synthesis is described where 1,6-heptadien4-ol is converted in eight operations to the desired products, as well as an improved process for the preparation of (2R-trans) and trans-(.+-.)-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetra hydro4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3carboxamide by a novel synthesis where 4-methyl-3-oxoN-phenylpentanamide is converted in eight operations to the desired product or alternatively 4-fluoro-.alpha.-[2methyl-1-oxopropyl]-.gamma.-oxo-N,.beta.-diphenylbenzen ebutaneamide is converted in one step to the desired product, and additionally, a process for preparing (2R-trans)-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetrahy dro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1Hpyrrole-3-carboxamide from (R)-4-cyano-3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]butanoic acid, as well as other valuable intermediates used in the processes.

  本文描述了一种改进的方法，通过新型合成将1,6-庚二烯-4-醇转化为所需产物，制备了转-6-[2-(取代吡咯-1-基)烷基]吡喃-2-酮，共进行了八个操作。此外，还描述了一种改进的方法，通过新型合成将4-甲基-3-氧代N-苯基戊酰胺转化为所需产物，或者通过一步将4-氟-α-[2-甲基-1-氧代丙基]-γ-氧代-N，β-二苯基苯丁烷酰胺转化为所需产物，制备了(2R-转型)和转型-(±)-5-(4-氟苯基)-2-(1-甲基乙基)-N，4-二苯基-1-[2-(四氢-4-羟基-6-氧代-2H-吡喃-2-基)乙基]-1H-吡咯-3-羧酰胺。此外，还提供了一种从(R)-4-氰基-3-[[(1,1-二甲基乙基)二甲基硅氧基]丁酸制备(2R-转型)-5-(4-氟苯基)-2-(1-甲基乙基)-N，4-二苯基-1-[2-(四氢-4-羟基-6-氧代-2H-吡咯-2-基)乙基]-1H-吡咯-3-羧酰胺的方法，以及用于制备这些化合物的其他有价值的中间体。
• Process for trans-6-(2-substituted-pyrrol-1-yl)alkyl)pyran-2-one
  申请人：Warner-Lambert Company

  公开号：US05124482A1

  公开（公告）日：1992-06-23

  An improved process for the preparation of trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-ones by a novel synthesis is described where 1,6-heptadien-4-ol is converted in eight operations to the desired products, as well as an improved process for the preparation of (2R-trans) and trans(.+-.)-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetrah ydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide by a novel synthesis where 4-methyl-3-oxo-N-phenylpentanamide is converted in eight operations to the desired product or alternatively 4-fluoro-.alpha.-[2-methyl-1-oxopropyl]-.gamma.-oxo-N,.beta.-diphenylbenze nebutaneamide is converted in one step to the desired product, and additionally, a process for preparing (2R-trans)-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetrahy dro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide from (R)-4-cyano-3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]butanoic acid, as well as other valuable intermediates used in the processes.

  本发明描述了一种改进的方法，通过一种新的合成方法，将1,6-庚二烯-4-醇转化为所需的产物，从而制备出改良的转-6-[2-(取代吡咯-1-基)烷基]吡喃-2-酮。此外，本发明还描述了一种改进的方法，通过一种新的合成方法，将4-甲基-3-氧代-N-苯基戊酰胺在八个步骤中转化为所需的产物，或者将4-氟-α-[2-甲基-1-氧代丙基]-γ-氧代-N，β-二苯基苯基丁酰胺在一步中转化为所需的产物，用于制备(2R-转)-5-(4-氟苯基)-2-(1-甲基乙基)-N，4-二苯基-1-[2-(四氢-4-羟基-6-氧代-2H-吡喃-2-基)乙基]-1H-吡咯-3-羧酰胺，以及用于该过程中使用的其他有价值的中间体。此外，本发明还描述了一种从(R)-4-氰基-3-[[(1,1-二甲基乙基)二甲基硅氧基]丁酸制备(2R-转)-5-(4-氟苯基)-2-(1-甲基乙基)-N，4-二苯基-1-[2-(四氢-4-羟基-6-氧代-2H-吡喃-2-基)乙基]-1H-吡咯-3-羧酰胺的方法。
• Inhibitors of cholesterol biosynthesis. 1. trans-6-(2-Pyrrol-1-ylethyl)-4-hydroxypyran-2-ones, a novel series of HMG-CoA reductase inhibitors. 1. Effects of structural modifications at the 2- and 5-positions of the pyrrole nucleus
  作者：Bruce D. Roth、D. F. Ortwine、M. L. Hoefle、C. D. Stratton、D. R. Sliskovic、M. W. Wilson、R. S. Newton

  DOI：10.1021/jm00163a005

  日期：1990.1

  A novel series of trans-6-(2-pyrrol-1-ylethyl)-4-hydroxypyran-2-ones and their dihydroxy acid derivatives were prepared and evaluated for their ability to inhibit the enzyme HMG-CoA reductase in vitro. A systematic study of substitution at the 2- and 5-positions of the pyrrole ring revealed that optimum potency was realized with the 2-(4-fluorophenyl)-5-isopropyl derivative 8x, which possessed 30% of the in vitro activity of the potent fungal metabolite compactin (I). A molecular modeling analysis led to the description of a pharmacophore model characterized by (A) length limits of 5.9 and 3.3 A for the 2- and 5-substituents, respectively, as well as an overall width limit of 10.6 A across the pyrrole ring from the 2- to the 5-substituent and (B) an orientation of the ethyl(ene) bridge to the 4-hydroxypyran-2-one ring nearly perpendicular to the planes of the parent pyrrole, hexahydronaphthalene, and phenyl rings of the structures examined (Figure 3, theta = 80-110 degrees). Attempts to more closely mimic compactin's polar isobutyric ester side chain with the synthesis of 2-phenylpyrroles containing polar phenyl substituents resulted in analogues with equal or slightly reduced potencies when compared to the 2-[(unsubstituted or 4-fluoro)phenyl]pyrroles, supporting the hypothesis that inhibitory potency is relatively insensitive to side-chain polarity or charge distribution in this area.