2-(2,4,5-trifluoro-3-methylphenyl)-4,4-dimethyl-2-oxazoline | 132630-83-2

• 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: 2-(2,4,5-trifluoro-3-methylphenyl)-4,4-dimethyl-2-oxazoline
• 英文别名: 2-(3-methyl-2,4,5-trifluoro-phenyl)-4,4-dimethyl-oxazoline；2-(2,4,5-Trifluoro-3-methylphenyl)-4,5-dihydro-4,4-dimethyloxazole；4,4-dimethyl-2-(2,4,5-trifluoro-3-methylphenyl)-5H-1,3-oxazole
• CAS: 132630-83-2
• 化学式: C₁₂H₁₂F₃NO
• 分子量: 243.229
• InChiKey: SLWCAJZXIPUHCV-UHFFFAOYSA-N

物化性质

• 沸点：
  284.8±40.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  21.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(2,4,5-trifluoro-3-methylphenyl)-4,4-dimethyl-2-oxazoline 在 盐酸 作用下， 以 水 为溶剂， 反应 8.0h， 以92%的产率得到2,4,5-三氟-3-甲基苯甲酸
  参考文献：
  名称：

  Synthesis of mono- and di-substituted 2,4,5-trifluorobenzoic acid synthons, key precursors for biologically active 6-fluoroquinolones

  摘要：

  In the search for new potent antiparasitical fluoroquinolones, a QSAR analysis by molecular connectivity led to the design of R-5 (Me or Et)/R-8 (MeO, Me or Et)-substituted analogs of the most powerful antibacterial or antiparasitical fluoroquinolones known so far. Unfortunately, the synthetic schemes that were elaborated in literature for 3- and 3,6-di-substiluted 2,4,5-trifluorobenzoic acids, the key precursors of the target R-5/R-8-substituted 6-fluoroquinolones, led in our hands to poor yields and/or to inextricable mixtures of derivatives. This led us to reinvestigate the key alkylation steps or the 2,4,5-trifluorophenyl-oxazoline synthons and the subsequent deprotection of their oxazoline into acid with the aim of optimising the syntheses of 3- and 3,6-di-Substituted 2.4,5-trifluorobenzoic acids, which constitute the entries to our target derivatives. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2005.06.078
• 作为产物：
  描述：

  2,4,5-三氟苯甲酰氯 在 氯化亚砜 、 lithium diisopropyl amide 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 生成 2-(2,4,5-trifluoro-3-methylphenyl)-4,4-dimethyl-2-oxazoline
  参考文献：
  名称：

  5-甲基-4-氧代喹啉羧酸的合成

  摘要：

  制备了一系列5-甲基-4-氧代-3-喹啉羧酸，其中八个位置被氟，氯，甲基或氢取代。这些喹诺酮是由衍生自恶唑啉8和16的合适的2-甲基-3,4,6-三氟苯甲酸合成的。恶唑啉部分既是邻位导向基团（在可行的情况下）又是保护基团；三甲基甲硅烷基部分被用来封闭分子中最酸性的位点。

  DOI：

  10.1002/jhet.5570270616

文献信息

• Studies on Quinolone Antibacterials. IV. Structure-Activity Relationships of Antibacterial Activity and Side Effects for 5- or 8-Substituted and 5,8-Disubstituted-7-(3-amino-1-pyrrolidinyl)-1-cyclopropyl-1,4-dihydro-4-oxoquinoline-3-carboxylic Acids.
  作者：Toshihiko YOSHIDA、Yoichi YAMAMOTO、Hitomi ORITA、Masato KAKIUCHI、Yoshie TAKAHASHI、Masakazu ITAKURA、Noriyuki KADO、Kazuya MITANI、Shingo YASUDA、Hideo KATO、Yasuo ITOH

  DOI：10.1248/cpb.44.1074

  日期：——

  A series of 7-(3-amino-1-pyrrolidinyl)-1-cyclopropyl-1, 4-dihydro-4-oxoquinoline-3-carboxylic acids bearing various substituents (H, F, Cl, Me, OH, OMe, OEt, OCH2F, OCHF2, OCF3, SMe) at the C-8 position was prepared and evaluated for in vitro antibacterial activity against both standard laboratory strains and bacteria resistant to quinolones such as ciprofloxacin (CPFX, 1) and ofloxacin (OFLX, 2) from clinical isolates. The 8-methyl (8a), 8-fluoro (9a), 8-chloro (10a) and 8-methoxy (12a) compounds were 4 times more potent than CPEX (1) against both gram-positive and gram-negative bacteria. But these four compounds caused injury to the chromosomes of mammalian cells at a concentration of 100 μg/ml. Next, a series of quinolones having various substituents (H, Cl, Me, NH2, NHMe, NMe2) at the C-5 position was prepared and evaluated for antibacterial activity and injurious effect on the chromosome. We found that the 5-amino-8-methyl compound (8d) showed strong antibacterial activity (in vitro antibacterial activity of 8d is 4 times more potent than that of CPFX (1) against both gram-positive and gram-negative bacteria), reduced injury to the chromosome, and reduced quinolone-type toxicity (free from both photoxicity at a dosage of 30 mg/kg in guinea pigs (i.v.) and convulsion-inducing activity when coadministered with fenbufen at a dosage of 100 mg/kg in mice (i.p.)).

  一系列带有各种取代基（H、F、Cl、Me、OH、OMe、OEt）的 7-(3-氨基-1-吡咯烷基)-1-环丙基-1, 4-二氢-4-氧代喹啉-3-羧酸，OCH2F，OCHF2，OCF3，SMe）在C-8位被制备并评估其对标准实验室菌株和对喹诺酮类药物（例如环丙沙星（CPFX，1）和氧氟沙星（OFLX，2））耐药的细菌的体外抗菌活性。临床分离株。 8-甲基 (8a)、8-氟 (9a)、8-氯 (10a) 和 8-甲氧基 (12a) 化合物对革兰氏阳性菌和革兰氏阴性菌的作用比 CPEX (1) 强 4 倍。但这四种化合物在浓度为100μg/ml时就会对哺乳动物细胞的染色体造成损伤。接下来，制备了一系列在C-5位具有各种取代基（H、Cl、Me、NH2、NHMe、NMe2）的喹诺酮类药物，并评价其抗菌活性和对染色体的损伤作用。我们发现5-氨基-8-甲基化合物（8d）表现出很强的抗菌活性（8d的体外抗菌活性对革兰氏阳性菌和革兰氏阴性菌均比CPFX（1）强4倍），减少对染色体的损伤，并降低喹诺酮类毒性（在豚鼠（静脉注射）剂量为 30 mg/kg 时无光毒性，在小鼠中与芬布芬以 100 mg/kg 剂量共同给药时无惊厥诱导活性） （ip））。
• Antibacterial agents
  申请人：Warner-Lambert Company

  公开号：US04920120A1

  公开（公告）日：1990-04-24

  Novel naphthyridine-, and quinolinecarboxylic acids as antibacterial agents are described as well as methods for their manufacture, formulation, and use in treating bacterial infections including the description of certain novel intermediates used in the manufacture of the antibacterial agents.

  本文描述了新型萘啶和喹啉羧酸作为抗菌剂的用途，以及它们的制造、配方和用于治疗细菌感染的方法，包括描述用于制造抗菌剂的某些新型中间体。
• ANTIBACTERIAL AGENTS
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0398967A1

  公开（公告）日：1990-11-28
• US4920120A
  申请人：——

  公开号：US4920120A

  公开（公告）日：1990-04-24
• US5585491A
  申请人：——

  公开号：US5585491A

  公开（公告）日：1996-12-17