吡唑并[1,5-a]吡啶-2,3-二甲酸二乙酯 | 1226776-92-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 中文名称: 吡唑并[1,5-a]吡啶-2,3-二甲酸二乙酯
• 中文别名: 吡唑并[1,5-A]吡啶-2,3-二甲酸二乙酯
• 英文名称: diethyl pyrazolo[1,5-a]pyridine-2,3-dicarboxylate
• CAS: 1226776-92-6
• 化学式: C₁₃H₁₄N₂O₄
• 分子量: 262.265
• InChiKey: NAXXLPOSQSYXEK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  69.9
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  吡唑并[1,5-a]吡啶-2,3-二甲酸二乙酯 在 copper(l) iodide 、 bis(2,2,6,6-tetramethylpiperidinyl)zinc, lithium chloride, magnesium chloride complex 、 碘 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 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
• 作为产物：
  描述：

  1-氨基吡啶碘 、 丁炔二酸二乙酯 在 氧气 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 24.0h， 以75%的产率得到吡唑并[1,5-a]吡啶-2,3-二甲酸二乙酯
  参考文献：
  名称：

  官能化吡唑并[1,5-a]吡啶的合成：N-氨基吡啶和α，β-不饱和羰基化合物/烯烃的[3 + 2]环加成反应在室温下

  摘要：

  摘要 描述了通过N-氨基吡啶与α，β-不饱和羰基化合物或吸电子烯烃的氧化[3 + 2]环加成反应，合成官能化的吡唑并[1,5- a ]吡啶。反应在室温下在无金属条件下在N-甲基吡咯烷酮作为溶剂中进行。 描述了通过N-氨基吡啶与α，β-不饱和羰基化合物或吸电子烯烃的氧化[3 + 2]环加成反应，合成官能化的吡唑并[1,5- a ]吡啶。反应在室温下在无金属条件下在N-甲基吡咯烷酮作为溶剂中进行。

  DOI：

  10.1055/s-0036-1588753

文献信息

• Palladium-Catalyzed Direct Arylations of 1,2-Azolo[1,5-<i>a</i>]pyridines using Copper(I) Chloride as a Lewis Acid Activator and the Synthesis of 2,6-Disubstituted Pyridines
  作者：Kyung Hwan Oh、Seong Min Kim、Mi Jung Lee、Jin Kyoon Park

  DOI：10.1002/adsc.201500726

  日期：2015.12.14

  A direct method for the arylation of 1,2-azolo[1,5-a]pyridines has been developed. In the process, the fused pyridines react with aryl halides in the presence of the palladium complex Pd(OAc)2(Phen) as a catalyst and copper(I) chloride (CuCl) as a Lewis acid to form arylated derivatives. While pyrazolo[1,5-a]pyridines and [1,2,4]triazolo[1,5-a]pyridines are arylated at ortho-positions of their pyridine

  已经开发出一种直接的方法用于1，2-氮杂[1，5- a ]吡啶的芳基化。在该方法中，在作为催化剂的钯配合物Pd（OAc）2（Phen）和作为路易斯酸的氯化铜（I）（CuCl）存在下，稠合吡啶与芳基卤化物反应形成芳基化衍生物。虽然吡唑并[1,5- a ]吡啶和[1,2,4]三唑并[1,5- a ]吡啶使用这种方法在其吡啶环的邻位芳基化，但原位形成的C发生-7个芳基化的[1，5- a ]吡啶，生成2，6-二取代的吡啶。同样，用二异丙基氨基锂（LDA）处理后，C-7芳基吡唑并[1,5- a]吡啶-3-羧酸酯反应生成不同取代的2,6-二取代吡啶。最后，通过两步顺序完成顺序的C-3芳基化反应，该顺序涉及吡唑并[1,5 - a ]吡啶-3-羧酸酯的水解，然后与芳基溴化物进行双金属Pd / Cu催化的脱羧偶联反应。
• Direct C7‐H Arylation of Pyrazolo[1,5‐<i>a</i>]azines with Aryl Chlorides
  作者：Thanh V. Q. Nguyen

  DOI：10.1002/chem.202301485

  日期：2023.8.10

  A new protocol for the palladium-catalyzed C−H arylation of pyrazolo[1,5-a]azines, using low-cost and abundant (hetero)aryl chlorides as the coupling partners, and without any stoichiometric metal additives is reported. The structural motif of coupling products can be found in many drugs and organic materials.

  报道了一种钯催化吡唑并[1,5- a ]嗪的C−H芳基化的新方案，使用低成本且丰富的（杂）芳基氯化物作为偶联伙伴，并且没有任何化学计量的金属添加剂。偶联产物的结构基序可以在许多药物和有机材料中找到。
• 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.
• 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 Functionalized Pyrazolo[1,5-a]pyridines: [3+2] Cycloaddition of N-Aminopyridines and α,β-Unsaturated Carbonyl Compounds/Alkenes at Room Temperature
  作者：Chitrakar Ravi、Supravat Samanta、Darapaneni Mohan、N. Reddy、Subbarayappa Adimurthy

  DOI：10.1055/s-0036-1588753

  日期：2017.6

  through oxidative [3+2] cycloaddition of N-aminopyridines with α,β-unsaturated carbonyl compounds or electron-withdrawing olefins is described. The reactions proceed in N-methylpyrrolidone as the solvent under metal-free conditions at room temperature. The synthesis of functionalized pyrazolo[1,5-a]pyridines through oxidative [3+2] cycloaddition of N-aminopyridines with α,β-unsaturated carbonyl compounds

  摘要 描述了通过N-氨基吡啶与α，β-不饱和羰基化合物或吸电子烯烃的氧化[3 + 2]环加成反应，合成官能化的吡唑并[1,5- a ]吡啶。反应在室温下在无金属条件下在N-甲基吡咯烷酮作为溶剂中进行。 描述了通过N-氨基吡啶与α，β-不饱和羰基化合物或吸电子烯烃的氧化[3 + 2]环加成反应，合成官能化的吡唑并[1,5- a ]吡啶。反应在室温下在无金属条件下在N-甲基吡咯烷酮作为溶剂中进行。