ethyl 3-(2-chloro-4,5-difluorophenyl)-3-oxopropanoate | 121872-97-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 3-(2-chloro-4,5-difluorophenyl)-3-oxopropanoate
• 英文别名: 2-chloro-4,5-difluoro-β-oxobenzenepropanoic acid ethyl ester；ethyl 2-chloro-4,5-difluorobenzoylacetate；Ethyl 3-(2-chloro-4,5-difluorophenyl)-3-oxopropionate
• CAS: 121872-97-7
• 化学式: C₁₁H₉ClF₂O₃
• 分子量: 262.64
• InChiKey: QMQGGCRCCRHQNF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 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 3-(2-chloro-4,5-difluorophenyl)-3-oxopropanoate 在 盐酸 、 乙酸酐 、 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：

  2-氯-4,5-二氟苯甲酰氯 在 2-甲基咪唑 、 4-甲基苯磺酸吡啶 、 magnesium chloride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 18.0h， 生成 ethyl 3-(2-chloro-4,5-difluorophenyl)-3-oxopropanoate
  参考文献：
  名称：

  AN ALTERNATIVE SYNTHESIS OF ETHYL 3-(2-CHLORO-4,5-DIFLUOROPHENYL)-3-OXOPROPIONATE AND ETHYL 3-(2,6-DICHLORO-5-FLUOROPYRIDIN-3-YL)-3-OXOPROPIONATE

  摘要：

  DOI：

  10.1080/00304949709355192

文献信息

• Intermediates for preparing 1,4-dihydro-4-oxo-quinoline-3-carboxylic acid esters
  申请人：PFIZER INC.

  公开号：EP0342849A3

  公开（公告）日：1990-03-14

  Compounds of the formula: wherein Y is OR¹, fluoro, chloro, methyl, R¹, and R³ are independently selected from hydrogen and C₁-C₄ alkyl, R² is C₁-C₄ alkyl and X is fluoro, chloro or bromo, with the proviso that when Y is OH, X cannot be bromo and with the proviso that X can be fluoro only if R² is methyl.

  式的化合物： 其中Y为OR¹，氟，氯，甲基， R¹和R³分别选自氢和C₁-C₄烷基，R²为C₁-C₄烷基，X为氟，氯或溴，但当Y为OH时，X不能为溴，且X只能为氟当且仅当R²为甲基。
• Process for preparing 2-chloro-4,5-difluorobenzoic acid
  申请人：American Cyanamid Company

  公开号：US04833270A1

  公开（公告）日：1989-05-23

  This disclosure describes a novel process for preparing 2-chloro-4,5-difluorobenzoic acid which is useful in the preparation of 7-(substituted)piperazinyl-1-substituted-6-fluoro-1,4-dihydro-4-oxo-3-quin oli necarboxylic acid antibacterial agents.

  这份披露描述了一种新颖的制备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-喹啉羧酸抗菌剂中很有用。
• Preparation of beta-ketoesters useful in preparing quinolone antibiotics
  申请人：Pfizer Inc.

  公开号：US05380860A1

  公开（公告）日：1995-01-10

  A method for preparing a compound of the formula ##STR1## wherein Q is C--H or N; R.sup.1 is C.sub.1-C.sub.4 alkyl, benzyl or p-nitrobenzyl and X and Y are independently selected from fluoro and chloro comprising reacting a compound of the formula ##STR2## wherein Q is >C--H or N; X and Y are independently selected from fluoro and chloro; and Z is fluoro, chloro, 1-imidazolyl or substituted 1-imidazolyl, wherein the 1-imidazolyl group is substituted with one or two substituents independently selected from C.sub.1 to C.sub.4 alkyl, with a compound of the formula [M.sup.n+ ].sub.p [V.sup.p- ].sub.n wherein M is an alkaline earth metal, Cu or Mn, n is 2, V.sup.p-, wherein p is 1 or 2, is an anion of the formula ##STR3## or a dianion of the formula ##STR4## and R.sup.1 is C.sub.1 to C.sub.6 alkyl or paranitrobenzyl, with the proviso that when Z is 1-imidazolyl or substituted 1-imidazole, M is magnesium, copper or manganese and with the proviso that when Z is fluoro, chloro or bromo, V.sup.p- is a dianion of the formula V(b).

  一种制备化合物的方法，其化学式为##STR1##其中Q为C--H或N；R.sup.1为C.sub.1-C.sub.4烷基、苄基或对硝基苄基，X和Y分别选自氟和氯，包括反应化合物的方法的步骤##STR2##其中Q为>C--H或N；X和Y分别选自氟和氯；Z为氟、氯、1-咪唑基或取代的1-咪唑基，其中1-咪唑基上取代有一个或两个取自C.sub.1到C.sub.4烷基的取代基，与化合物反应的是化学式为[M.sup.n+ ].sub.p [V.sup.p- ].sub.n的化合物，其中M为碱土金属、铜或锰，n为2，V.sup.p-，其中p为1或2，是化学式为##STR3##的阴离子或化学式为##STR4##的二阴离子，R.sup.1为C.sub.1到C.sub.6烷基或对硝基苄基，但是当Z为1-咪唑基或取代的1-咪唑基时，M为镁、铜或锰，并且当Z为氟、氯或溴时，V.sup.p-为化学式V(b)的二阴离子。
• 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.

  公开了以下公式的氟化苯甲酰化合物：##STR1##其中Q是较低的烷基基团、卤素原子、--CH.sub.2 CO.sub.2 R.sup.1其中R.sup.1是较低的烷基基团，或##STR2##其中R.sup.2和R.sup.3中的每一个都是较低的烷基基团。
• Fluorinated benzoyl compounds
  申请人：Asahi Glass Company Ltd.

  公开号：US05093515A1

  公开（公告）日：1992-03-03

  A 2-chloro-4,5-difluorobenzoyl compound of the formula: ##STR1## wherein R.sup.2 is a lower alkyl group, and R.sup.7 is a 2,4-difluorophenyl group or a 4-fluorophenyl group.

  公式为：##STR1## 其中R.sup.2是较低的烷基基团，R.sup.7是2,4-二氟苯基基团或4-氟苯基基团的2-氯-4,5-二氟苯甲酰化合物。