ethyl 2-(3-bromo-2-chloro-4,5-difluorobenzoyl)acetate | 112062-53-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 2-(3-bromo-2-chloro-4,5-difluorobenzoyl)acetate
• 英文别名: ethyl 3-bromo-2-chloro-4,5-difluorobenzoyl-acetate；ethyl 3-(3-bromo-2-chloro-4,5-difluorophenyl)-3-oxopropanoate
• CAS: 112062-53-0
• 化学式: C₁₁H₈BrClF₂O₃
• 分子量: 341.537
• InChiKey: PLXLBLOMIGWCNY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 2-(3-bromo-2-chloro-4,5-difluorobenzoyl)acetate 在 盐酸 、 乙酸酐 、 potassium carbonate 、 溶剂黄146 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-(5-amino-2,4-difluorophenyl)-8-bromo-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  A Novel Antibacterial 8-Chloroquinolone with a Distorted Orientation of the N1-(5-Amino-2,4-difluorophenyl) Group

  摘要：

  Fluoroquinolones represent a major class of antibacterial agents with great therapeutic potential. In this study, we designed m-aminophenyl groups as novel N-1 substituents of naphthyridones and quinolones. Among newly synthesized compounds, 7-(3-aminoazetidin-1-yl)-1-(5-amino-2,4-difluorophenyl)-8-chloro-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (4) has extremely potent antibacterial activities against Gram (+) as well as Gram (-) bacteria. This compound is significantly more potent than trovafloxacin against clinical isolates: 30 times against Streptococcus pneumoniae and 128 times against methicillin resistant Staphylococcus aureus. The structure-activity relationship (SAR) study revealed that a limited combination of 1-(5-amino-2,4-difluorophenyl) group, 7-(azetidin-1-yl) group, and 8-Cl atom (or Br atom or Me group) gave potent antibacterial activity. An X-ray crystallographic study of a 7-(3-ethylaminoazetidin-1-yl)-8-chloro derivative demonstrated that the N-1 aromatic group was remarkably distorted out of the core quinolone plane by steric repulsion between the C-8 C1 atom and the N-1 substituent. Furthermore, a molecular modeling study of 4 and its analogues demonstrated that a highly distorted orientation was induced by a steric hindrance of the C-8 substituent, such as Cl, Br, or a methyl group. Thus, their highly strained conformation should be a key factor for the potent antibacterial activity.

  DOI：

  10.1021/jm0205090
• 作为产物：
  描述：

  diethyl 2-(3-bromo-2-chloro-4,5-difluorobenzoyl)malonate 在 对甲苯磺酸 作用下， 以 水 为溶剂， 生成 ethyl 2-(3-bromo-2-chloro-4,5-difluorobenzoyl)acetate
  参考文献：
  名称：

  Benzoylacetic acid ester derivatives and process for their preparations

  摘要：

  本发明涉及某些新颖的苯甲酰乙酸酯衍生物（I），其可用作合成抗菌剂的中间体。其中，R为低碳烷基基团，X为卤素原子，Y为氯或溴原子。

  公开号：

  US04788320A1

文献信息

• Process for the preparation of quinolonecarboxylic acid derivatives
  申请人：KYORIN PHARMACEUTICAL CO., LTD.

  公开号：EP0230946A2

  公开（公告）日：1987-08-05

  The present invention is concerned with certain novel process for the preparation of quinolonecarboxylic acid derivatives of the following formula, wherein R¹ is a lower alkyl group, X is a chlorine or bromine atom and Y is a halogen atom, which are useful intermediates for the synthesis of antibacterial agents.

  本发明涉及制备下式喹啉羧酸衍生物的某些新工艺，其中 R¹ 为低级烷基，X 为氯原子或溴原子，Y 为卤素原子，这些衍生物是合成抗菌剂的有用中间体。
• Benzoylacetic acid ester derivatives and process for their preparation
  申请人：KYORIN PHARMACEUTICAL CO., LTD.

  公开号：EP0230948A2

  公开（公告）日：1987-08-05

  The present invention is concerned with certain novel benzoylacetic acid ester derivatives (I) which are useful as a intermediates for synthesis of antibacterial agests. wherein R is a lower alkyl group, X is a halogen atom and Y is a chlorine or bromine atom.

  本发明涉及某些新型苯甲酰乙酸酯衍生物 (I)，它们可用作合成抗菌剂的中间体。 其中 R 是低级烷基，X 是卤素原子，Y 是氯原子或溴原子。
• EP230946
  申请人：——

  公开号：——

  公开（公告）日：——
• IRIKURA, TSUTOMU;SUDZUEH, SEHJGO;MURAYAMA, SATORU;XIRAI, KEHJDZI;ISIDZAKI+
  作者：IRIKURA, TSUTOMU、SUDZUEH, SEHJGO、MURAYAMA, SATORU、XIRAI, KEHJDZI、ISIDZAKI+

  DOI：——

  日期：——
• US4788320A
  申请人：——

  公开号：US4788320A

  公开（公告）日：1988-11-29