methyl {3-[4-(Propyloxy)-2-(trifluoromethyl)phenyl]-5-isoxazolyl}acetate | 1268385-34-7

• 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: methyl {3-[4-(Propyloxy)-2-(trifluoromethyl)phenyl]-5-isoxazolyl}acetate
• 英文别名: methyl 2-(3-(4-propoxy-2-(trifluoromethyl)phenyl)isoxazol-5-yl)acetate；methyl {3-[4-(propyloxy)-2-(trifluoromethyl)phenyl]-5-isoxazolyl}acetate；Methyl {3-[4-(propyloxy)-2-(trifluoromethyl)phenyl]-5-isoxazolyl}acetate；methyl 2-[3-[4-propoxy-2-(trifluoromethyl)phenyl]-1,2-oxazol-5-yl]acetate
• CAS: 1268385-34-7
• 化学式: C₁₆H₁₆F₃NO₄
• 分子量: 343.303
• InChiKey: LYUQMWPEEBFVEJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  61.6
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl {3-[4-(Propyloxy)-2-(trifluoromethyl)phenyl]-5-isoxazolyl}acetate 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 作用下， 以 四氯化碳 为溶剂， 反应 5.0h， 以57%的产率得到methyl 2-bromo-2-(3-(4-propoxy-2-(trifluoromethyl)phenyl)isoxazol-5-yl)acetate
  参考文献：
  名称：

  Imidazopyridazine Compounds for Treating Viral Infections

  摘要：

  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。

  公开号：

  US20110052534A1
• 作为产物：
  描述：

  在 高碘酸 、 三乙胺 、 乙酰氯 、 pyridinium chlorochromate 作用下， 以 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 7.08h， 生成 methyl {3-[4-(Propyloxy)-2-(trifluoromethyl)phenyl]-5-isoxazolyl}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

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：
• 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.
• Imidazopyridazine Hepatitis C Virus Polymerase Inhibitors. Structure–Activity Relationship Studies and the Discovery of a Novel, Traceless Prodrug Mechanism
  作者：Martin Leivers、John F. Miller、Stephanie A. Chan、Ryan Lauchli、Sebastian Liehr、Wenyan Mo、Tony Ton、Elizabeth M. Turner、Michael Youngman、J. Greg Falls、Susan Long、Amanda Mathis、Jill Walker

  DOI：10.1021/jm401337x

  日期：2014.3.13

  By reducing the basicity of the core heterocycle in a series of HCV NS5B inhibitors, the hERG liability was reduced. The SAR was then systematically explored in order to increase solubility and enable dose escalation while retaining potency. During this exploration, a facile decarboxylation was noted and was exploited as a novel prodnig mechanism. The synthesis and characterization of these prodrugs and their utilization in chronic toxicity studies are presented.