3-(2-chloro-4,5-dilfuorophenyl)-3-oxo-2-(ethoxymethylene)propanoic acid ethyl ester | 121872-98-8

• 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: 3-(2-chloro-4,5-dilfuorophenyl)-3-oxo-2-(ethoxymethylene)propanoic acid ethyl ester
• 英文别名: 2-chloro-α-(ethoxymethylene)-4,5-difluoro-β-oxobenzenepropanoic acid, ethyl ester；ethyl 2-(2-chloro-4,5-difluorobenzoyl)-3-ethoxyacrylate；ethyl 2-(2-chloro-4,5-difluorobenzoyl)-3-ethoxyprop-2-enoate
• CAS: 121872-98-8
• 化学式: C₁₄H₁₃ClF₂O₄
• 分子量: 318.705
• InChiKey: OQAAFIHDFZXOOG-UHFFFAOYSA-N

物化性质

• 沸点：
  422.6±45.0 °C(Predicted)
• 密度：
  1.308±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(2-chloro-4,5-dilfuorophenyl)-3-oxo-2-(ethoxymethylene)propanoic acid ethyl ester 在 盐酸 、 potassium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 7-(3-Aminoazetidin-1-yl)-1-(5-amino-2,4-difluorophenyl)-6-fluoro-4-oxoquinoline-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：

  原甲酸三乙酯 、 ethyl 3-(2-chloro-4,5-difluorophenyl)-3-oxopropanoate 以 乙酸酐 为溶剂， 反应 2.0h， 以giving 16.59 g of the desired product as an oil的产率得到3-(2-chloro-4,5-dilfuorophenyl)-3-oxo-2-(ethoxymethylene)propanoic acid ethyl ester
  参考文献：
  名称：

  Process for preparing 2-chloro-4,5-difluorobenzoic acid

  摘要：

  本公开说明了一种新的制备2-氯-4,5-二氟苯甲酸的过程，该过程在制备7-(取代)piperazinyl-1-取代-6-氟-1,4-二氢-4-氧-3-喹啉羧酸类抗菌剂时有用。

  公开号：

  US04833270A1

文献信息

• Fluoronaphthyridines and -quinolones as antibacterial agents. 3. Synthesis and structure-activity relationships of new 1-(1,1-dimethyl-2-fluoroethyl), 1-[1-methyl-1-(fluoromethyl)-2-fluoroethyl], and 1-[1,1-(difluoromethyl)-2-fluoroethyl] substituted derivatives
  作者：P. Remuzon、D. Bouzard、P. Di Cesare、M. Essiz、J. P. Jacquet、J. R. Kiechel、B. Ledoussal、R. E. Kessler、J. Fung-Tomc

  DOI：10.1021/jm00105a006

  日期：1991.1

  prepared. Structure-activity relationship (SAR) studies indicated that the in vitro antibacterial potency was the following order: 1-(1,1-dimethyl-2-fluoroethyl) greater than 1-[1-methyl-1-(fluoromethyl)-2-fluoroethyl] greater than 1-[1,1-(difluoromethyl)-2-fluoroethyl] substituents. In the quinolone series the monofluoro-tert-butyl derivatives were found to possess better in vitro antibacterial activity

  制备了一系列新型的N-1-（单-，-（二-和-（三氟叔丁基）喹诺酮）和-萘吡啶类化合物，结构-活性关系（SAR）研究表明，体外抗菌能力是顺序如下：1-（1,1-二甲基-2-氟乙基）大于1- [1-甲基-1-（氟甲基）-2-氟乙基]大于1- [1,1-（二氟甲基）-2-在喹诺酮系列中，发现单氟叔丁基衍生物具有比非氟化叔丁基等效物更好的体外抗菌活性，其中1-氟叔丁基取代衍生物的体内PD50值反映了药代动力学行为和口服吸收不完全。
• Thiazolyl and oxazolyl[5,4-c]piperidyl-substituted quinolone-carboxylic
  申请人：Pfizer Inc.

  公开号：US05214051A1

  公开（公告）日：1993-05-25

  Thiazolyl and oxazolyl [5,4-c] piperidyl-substituted quinolone-carboxylic acids and related analogs thereof having antibacterial properties are disclosed.

  本发明揭示了具有抗菌性的噻唑基和氧唑基[5,4-c]哌啶取代的喹诺酸羧酸及其相关类似物。
• Process for preparing fluorinated benzoyl compounds
  申请人：Asahi Glass Company, Ltd.

  公开号：US04994610A1

  公开（公告）日：1991-02-19

  Fluorinated benzoyl compounds of the formula: ##STR1## wherein Q is a lower alkyl group, a halogen atom, --CH.sub.2 CO.sub.2 R.sup.1 wherein R.sup.1 is a lower alkyl group, or ##STR2## wherein each of R.sup.2 and R.sup.3 is a lower alkyl group, are disclosed.

  本发明涉及一种化合物，化学式为：##STR1## 其中Q是低碳基，卤素原子，--CH.sub.2 CO.sub.2 R.sup.1，其中R.sup.1是低碳基，或者##STR2## 其中R.sup.2和R.sup.3中的每一个都是低碳基。
• Heterocycylic-substituted quinoline-carboxylic acids
  申请人：Pfizer Inc.

  公开号：US05037834A1

  公开（公告）日：1991-08-06

  1-Substituted-6-fluoro-7-heterocyclic-1,4-dihydroquino-1-(or dihydronaphthyridin)-4-one carboxylic acids have antibacterial properties. The 7-heterocyclic group is a bicyclic group, one of the rings of which is saturated and the other ring of which is unsaturated.

  1-取代的6-氟-7-杂环-1,4-二氢喹诺-1-(或二氢萘啶)-4-酮羧酸具有抗菌性质。7-杂环基团是一个双环基团，其中一个环是饱和的，另一个环是不饱和的。
• Fluorinated benzoyl compounds
  申请人：Asahi Glass Company, Ltd.

  公开号：US05068449A1

  公开（公告）日：1991-11-26

  Fluorinated benzoyl compounds of the formula: ##STR1## wherein Q is a lower alkyl group, a halogen atom, --CH.sub.2 CO.sub.2 R.sup.1 wherein R.sup.1 is a lower alkyl group, or ##STR2## wherein each of R.sup.2 and R.sup.3 is a lower alkyl group.

  式为：##STR1## 的氟代苯甲酰化合物，其中Q是低碳基，卤素原子，--CH.sub.2 CO.sub.2 R.sup.1，其中R.sup.1是低碳基，或者##STR2##，其中R.sup.2和R.sup.3均为低碳基。