diethyl 7-(trifluoromethyl)pyrazolo[1,5-a]pyridine-2,3-dicarboxylate | 1385096-47-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 英文名称: diethyl 7-(trifluoromethyl)pyrazolo[1,5-a]pyridine-2,3-dicarboxylate
• 英文别名: Diethyl 7-(trifluoromethyl)pyrazolo[1,5-a]pyridine-2,3-dicarboxylate
• CAS: 1385096-47-8
• 化学式: C₁₄H₁₃F₃N₂O₄
• 分子量: 330.263
• InChiKey: QFSSKMHDLXJZFN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  69.9
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1-[[(4-甲基苯基)磺酰基]氨基]-吡啶鎓氢氧化物内盐 在 sodium carbonate 、 cesium fluoride 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 diethyl 7-(trifluoromethyl)pyrazolo[1,5-a]pyridine-2,3-dicarboxylate
  参考文献：
  名称：

  Synthesis of 7-trifluoromethylpyrazolo[1,5-a]pyridinedicarboxylate

  摘要：

  Two syntheses of 7-trifluoromethylpyrazolo[1,5-a]pyridine dicarboxylate have been described. Approach A utilizes a nucleophilic addition of a trifluoromethyl group to N-p-toluenesulfonyliminopyridinium ylide followed by aromatization and subsequent cycloaddition with diethyl acetylenedicarboxylate to give 1b in modest yield. Approach B involves a selective zincation of pyrazolopyridine dicarboxylate at the C-7 position with (TMP)(2)Zn center dot 2LiCl.2MgCl(2) followed by iodination and trifluoromethylation to give 1b in good yield. The process in approach B has been successfully demonstrated on scale. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2012.09.136

文献信息

• Hepatitis C Replication Inhibitors That Target the Viral NS4B Protein
  作者：John F. Miller、Pek Y. Chong、J. Brad Shotwell、John G. Catalano、Vincent W.-F. Tai、Jing Fang、Anna L. Banka、Christopher D. Roberts、Michael Youngman、Huichang Zhang、Zhiping Xiong、Amanda Mathis、Jeffery J. Pouliot、Robert K. Hamatake、Daniel J. Price、John W. Seal、Lisa L. Stroup、Katrina L. Creech、Luz H. Carballo、Dan Todd、Andrew Spaltenstein、Sylvia Furst、Zhi Hong、Andrew J. Peat

  DOI：10.1021/jm400125h

  日期：2014.3.13

  We describe the preclinical development and in vivo efficacy of a novel chemical series that inhibits hepatitis C virus replication via direct interaction with the viral nonstructural protein 4B (NS4B). Significant potency improvements were realized through isosteric modifications to our initial lead la. The temptation to improve antiviral activity while compromising physicochemical properties was tempered by the judicial use of ligand efficiency indices during lead optimization. In this manner, compound la was transformed into (+)-28a which possessed an improved antiviral profile with no increase in molecular weight and only a modest elevation in lipophilicity. Additionally, we employed a chimeric "humanized" mouse model of HCV infection to demonstrate for the first time that a small molecule with high in vitro affinity for NS4B can inhibit viral replication in vivo. This successful proof-of-concept study suggests that drugs targeting NS4B may represent a viable treatment option for curing HCV infection.
• Synthesis of 7-trifluoromethylpyrazolo[1,5-a]pyridinedicarboxylate
  作者：Pek Chong、Roman Davis、Vassil Elitzin、Mark Hatcher、Bing Liu、Matthew Salmons、Elie Tabet

  DOI：10.1016/j.tetlet.2012.09.136

  日期：2012.12

  Two syntheses of 7-trifluoromethylpyrazolo[1,5-a]pyridine dicarboxylate have been described. Approach A utilizes a nucleophilic addition of a trifluoromethyl group to N-p-toluenesulfonyliminopyridinium ylide followed by aromatization and subsequent cycloaddition with diethyl acetylenedicarboxylate to give 1b in modest yield. Approach B involves a selective zincation of pyrazolopyridine dicarboxylate at the C-7 position with (TMP)(2)Zn center dot 2LiCl.2MgCl(2) followed by iodination and trifluoromethylation to give 1b in good yield. The process in approach B has been successfully demonstrated on scale. (C) 2012 Elsevier Ltd. All rights reserved.