bis(1,1-dimethylethyl) 1-(2-(methyloxy)-2-oxo-1-{3-[4-(propyloxy)-2-(trifluoromethyl)phenyl]-5-isoxazolyl}ethyl)-1,2-hydrazinedicarboxylate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: bis(1,1-dimethylethyl) 1-(2-(methyloxy)-2-oxo-1-{3-[4-(propyloxy)-2-(trifluoromethyl)phenyl]-5-isoxazolyl}ethyl)-1,2-hydrazinedicarboxylate
• 英文别名: Methyl 2-[(2-methylpropan-2-yl)oxycarbonyl-[(2-methylpropan-2-yl)oxycarbonylamino]amino]-2-[3-[4-propoxy-2-(trifluoromethyl)phenyl]-1,2-oxazol-5-yl]acetate；methyl 2-[(2-methylpropan-2-yl)oxycarbonyl-[(2-methylpropan-2-yl)oxycarbonylamino]amino]-2-[3-[4-propoxy-2-(trifluoromethyl)phenyl]-1,2-oxazol-5-yl]acetate
• 化学式: C₂₆H₃₄F₃N₃O₈
• 分子量: 573.566
• InChiKey: BALXCAAOJMGVII-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  40
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  bis(1,1-dimethylethyl) 1-(2-(methyloxy)-2-oxo-1-{3-[4-(propyloxy)-2-(trifluoromethyl)phenyl]-5-isoxazolyl}ethyl)-1,2-hydrazinedicarboxylate 在 氢溴酸 作用下， 以 溶剂黄146 为溶剂， 反应 3.0h， 以87%的产率得到methyl 2-hydrazinyl-2-(3-(4-propoxy-2-(trifluoromethyl)-phenyl)isoxazol-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：

  2-溴-5-氟三氟甲苯 在 N,N-二甲基丙烯基脲 、 N-氯代丁二酰亚胺 、 potassium tert-butylate 、 羟胺 、 异丙基氯化镁 、 lithium carbonate 、 高碘酸 、 三乙胺 、 乙酰氯 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 15.83h， 生成 bis(1,1-dimethylethyl) 1-(2-(methyloxy)-2-oxo-1-{3-[4-(propyloxy)-2-(trifluoromethyl)phenyl]-5-isoxazolyl}ethyl)-1,2-hydrazinedicarboxylate
  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