4-bromo-2-(trifluoromethyl)benzaldehyde oxime | 1174506-86-5

• 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: 4-bromo-2-(trifluoromethyl)benzaldehyde oxime
• 英文别名: 4-Bromo-2-trifluoromethyl-benzaldehyde Oxime；N-[[4-bromo-2-(trifluoromethyl)phenyl]methylidene]hydroxylamine
• CAS: 1174506-86-5
• 化学式: C₈H₅BrF₃NO
• 分子量: 268.033
• InChiKey: UKGKETNIHOSJDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  32.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-bromo-2-(trifluoromethyl)benzaldehyde oxime 在 potassium phosphate 、 N-氯代丁二酰亚胺 、 三甲基氯硅烷 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 氢溴酸 、 lithium carbonate 、 高碘酸 、 三乙胺 、 pyridinium chlorochromate 作用下， 以 1,4-二氧六环 、 甲基叔丁基醚 、 溶剂黄146 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 41.0h， 生成 methyl {3-[4-cyclopropyl-2-(trifluoromethyl)phenyl]-5-isoxazolyl}[2-(2,3-difluorophenyl)-5H-imidazo[4,5-d]pyridazin-5-yl]acetate
  参考文献：
  名称：

  Synthesis of HCV Replicase Inhibitors: Base-Catalyzed Synthesis of Protected α-Hydrazino Esters and Selective Aerobic Oxidation with Catalytic Pt/Bi/C for Synthesis of Imidazole-4,5-dicarbaldehyde

  摘要：

  A robust convergent synthesis of the prodrugs of HCV replicase inhibitors 1-5 is described. The central 5H-imidazo[4,S-d]pyridazine core was formed from acid-catalyzed cyclocondensation of an imidazole-4,5-dicarbaldehyde (20) and a alpha-hydrazino ester, generated in situ from the bis-BOC-protected precursors 25 and 33. The acidic conditions not only released the otherwise unstable alpha-hydrazino esters but also were the key to avoid facile decarboxylation to the parent drugs from the carboxylic ester prodrugs 1-5. The bis-BOC alpha-hydrazino esters 25 and 33 were prepared by addition of ester enolates (from 23 and 32) to di-tert-butyl azodicarboxylate via catalysis with mild inorganic bases, such as Li2CO3. A selective aerobic oxidation with catalytic 5% Pt-Bi/C in aqueous KOH was developed to provide the dicarbaldehyde 20 from the diol 27.

  DOI：

  10.1021/jo4014595
• 作为产物：
  描述：

  4-溴-2-(三氟甲基)苯甲醛,95 在 羟胺 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 以966 g的产率得到4-bromo-2-(trifluoromethyl)benzaldehyde oxime
  参考文献：
  名称：

  Synthesis of HCV Replicase Inhibitors: Base-Catalyzed Synthesis of Protected α-Hydrazino Esters and Selective Aerobic Oxidation with Catalytic Pt/Bi/C for Synthesis of Imidazole-4,5-dicarbaldehyde

  摘要：

  A robust convergent synthesis of the prodrugs of HCV replicase inhibitors 1-5 is described. The central 5H-imidazo[4,S-d]pyridazine core was formed from acid-catalyzed cyclocondensation of an imidazole-4,5-dicarbaldehyde (20) and a alpha-hydrazino ester, generated in situ from the bis-BOC-protected precursors 25 and 33. The acidic conditions not only released the otherwise unstable alpha-hydrazino esters but also were the key to avoid facile decarboxylation to the parent drugs from the carboxylic ester prodrugs 1-5. The bis-BOC alpha-hydrazino esters 25 and 33 were prepared by addition of ester enolates (from 23 and 32) to di-tert-butyl azodicarboxylate via catalysis with mild inorganic bases, such as Li2CO3. A selective aerobic oxidation with catalytic 5% Pt-Bi/C in aqueous KOH was developed to provide the dicarbaldehyde 20 from the diol 27.

  DOI：

  10.1021/jo4014595

文献信息

• Imidazopyridazine Compounds for Treating Viral Infections
  申请人：Leivers Martin

  公开号：US20110052534A1

  公开（公告）日：2011-03-03

  Disclosed are compounds and compositions of Formula (I), pharmaceutically acceptable salts and solvates thereof, and their preparation and uses for treating viral infections mediated at least in part by a virus in the Flaviviridae family of viruses:

  揭示了化合物和Formula (I)的组成，其药用可接受的盐和溶剂，以及它们的制备和用于治疗至少部分由黄病毒科病毒介导的病毒感染的用途。
• Imidazo[4,5-d]Pyridazine Compounds For Treating Viral Infections
  申请人：Leivers Martin

  公开号：US20110053892A1

  公开（公告）日：2011-03-03

  Disclosed are compounds and compositions of Formula (I), pharmaceutically acceptable salts and solvates thereof, and their preparation and uses for treating viral infections mediated at least in part by a virus in the Flaviviridae family of viruses:

  本发明涉及公式(I)的化合物和组合物，其药学上可接受的盐和溶剂化物，以及它们的制备和用于治疗由Flaviviridae病毒家族中的病毒至少部分介导的病毒感染的用途：
• ANTI-VIRAL COMPOUNDS, COMPOSITIONS, AND METHODS OF USE
  申请人：Leivers Martin Robert

  公开号：US20090197880A1

  公开（公告）日：2009-08-06

  Disclosed are compounds of Formula (I), pharmaceutically acceptable salts and solvates thereof, compositions thereof, and methods for their preparation and uses for treating viral infections mediated at least in part by a virus in the Flaviviridae family of viruses.

  本发明涉及公式（I）的化合物，其药学上可接受的盐和溶剂化合物，以及其组合物的制备方法和用于治疗由黄病毒科病毒介导的至少部分病毒感染的用途。
• Synthesis of HCV Replicase Inhibitors: Base-Catalyzed Synthesis of Protected α-Hydrazino Esters and Selective Aerobic Oxidation with Catalytic Pt/Bi/C for Synthesis of Imidazole-4,5-dicarbaldehyde
  作者：Roy K. Bowman、Andrew D. Brown、Jannine H. Cobb、John F. Eaddy、Mark A. Hatcher、Martin R. Leivers、John F. Miller、Mark B. Mitchell、Daniel E. Patterson、Matthew A. Toczko、Shiping Xie

  DOI：10.1021/jo4014595

  日期：2013.12.6

  A robust convergent synthesis of the prodrugs of HCV replicase inhibitors 1-5 is described. The central 5H-imidazo[4,S-d]pyridazine core was formed from acid-catalyzed cyclocondensation of an imidazole-4,5-dicarbaldehyde (20) and a alpha-hydrazino ester, generated in situ from the bis-BOC-protected precursors 25 and 33. The acidic conditions not only released the otherwise unstable alpha-hydrazino esters but also were the key to avoid facile decarboxylation to the parent drugs from the carboxylic ester prodrugs 1-5. The bis-BOC alpha-hydrazino esters 25 and 33 were prepared by addition of ester enolates (from 23 and 32) to di-tert-butyl azodicarboxylate via catalysis with mild inorganic bases, such as Li2CO3. A selective aerobic oxidation with catalytic 5% Pt-Bi/C in aqueous KOH was developed to provide the dicarbaldehyde 20 from the diol 27.