pyridine-2-carboxylic acid [4-((R)-1-acetylpyrrolidin-2-yl)-5-fluoro-2-nitrophenyl]amide | 859538-52-6

• 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: pyridine-2-carboxylic acid [4-((R)-1-acetylpyrrolidin-2-yl)-5-fluoro-2-nitrophenyl]amide
• 英文别名: N-[4-[(2R)-1-acetylpyrrolidin-2-yl]-5-fluoro-2-nitrophenyl]pyridine-2-carboxamide
• CAS: 859538-52-6
• 化学式: C₁₈H₁₇FN₄O₄
• 分子量: 372.356
• InChiKey: HMEQEXOBISDZJO-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-hydroxy-(2-methoxymethyl)pyridine 、 pyridine-2-carboxylic acid [4-((R)-1-acetylpyrrolidin-2-yl)-5-fluoro-2-nitrophenyl]amide 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以90%的产率得到N-[4-[(2R)-1-acetylpyrrolidin-2-yl]-5-[6-(methoxymethyl)pyridin-3-yl]oxy-2-nitrophenyl]pyridine-2-carboxamide
  参考文献：
  名称：

  Enantioselective Pd-Catalyzed α-Arylation of N-Boc-Pyrrolidine: The Key to an Efficient and Practical Synthesis of a Glucokinase Activator

  摘要：

  A short and practical synthesis of glucokinase activator I was achieved utilizing a convergent strategy involving SNAr coupling of activated aryl fluoride 11 with hydroxypyridine 9. The key to the success of the synthesis was the development of a novel method for enantioselective formation of alpha-arylpyrrolidines during the course of the project. In this method, (-)-sparteine-mediated enantioselective lithiation of N-Boc-pyrrolidine was followed by in situ transmetalation to zinc and Pd-catalyzed coupling with aryl bromide 3, proceeding in 92% ee. This transformation allowed the preparation of compound I in a 31 % overall yield over-six steps.

  DOI：

  10.1021/jo8006804
• 作为产物：
  描述：

  pyridine-2-carboxylic acid [4-((R)-1-acetylpyrrolidin-2-yl)-3-fluorophenyl]amide 在 硫酸 、 硝酸 作用下， 以 二氯甲烷 为溶剂， 以1.97 kg的产率得到pyridine-2-carboxylic acid [4-((R)-1-acetylpyrrolidin-2-yl)-5-fluoro-2-nitrophenyl]amide
  参考文献：
  名称：

  Enantioselective Pd-Catalyzed α-Arylation of N-Boc-Pyrrolidine: The Key to an Efficient and Practical Synthesis of a Glucokinase Activator

  摘要：

  A short and practical synthesis of glucokinase activator I was achieved utilizing a convergent strategy involving SNAr coupling of activated aryl fluoride 11 with hydroxypyridine 9. The key to the success of the synthesis was the development of a novel method for enantioselective formation of alpha-arylpyrrolidines during the course of the project. In this method, (-)-sparteine-mediated enantioselective lithiation of N-Boc-pyrrolidine was followed by in situ transmetalation to zinc and Pd-catalyzed coupling with aryl bromide 3, proceeding in 92% ee. This transformation allowed the preparation of compound I in a 31 % overall yield over-six steps.

  DOI：

  10.1021/jo8006804

文献信息

• Enantioselective Pd-Catalyzed α-Arylation of <i>N</i>-Boc-Pyrrolidine: The Key to an Efficient and Practical Synthesis of a Glucokinase Activator
  作者：Artis Klapars、Kevin R. Campos、Jacob H. Waldman、Daniel Zewge、Peter G. Dormer、Cheng-yi Chen

  DOI：10.1021/jo8006804

  日期：2008.7.1

  A short and practical synthesis of glucokinase activator I was achieved utilizing a convergent strategy involving SNAr coupling of activated aryl fluoride 11 with hydroxypyridine 9. The key to the success of the synthesis was the development of a novel method for enantioselective formation of alpha-arylpyrrolidines during the course of the project. In this method, (-)-sparteine-mediated enantioselective lithiation of N-Boc-pyrrolidine was followed by in situ transmetalation to zinc and Pd-catalyzed coupling with aryl bromide 3, proceeding in 92% ee. This transformation allowed the preparation of compound I in a 31 % overall yield over-six steps.