N-[4-[(2R)-1-acetylpyrrolidin-2-yl]-5-[6-(methoxymethyl)pyridin-3-yl]oxy-2-nitrophenyl]pyridine-2-carboxamide | 1034497-97-6

• 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: N-[4-[(2R)-1-acetylpyrrolidin-2-yl]-5-[6-(methoxymethyl)pyridin-3-yl]oxy-2-nitrophenyl]pyridine-2-carboxamide
• CAS: 1034497-97-6
• 化学式: C₂₅H₂₅N₅O₆
• 分子量: 491.503
• InChiKey: BPOXFCOWAKNHCC-JOCHJYFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  140
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-[4-[(2R)-1-acetylpyrrolidin-2-yl]-5-[6-(methoxymethyl)pyridin-3-yl]oxy-2-nitrophenyl]pyridine-2-carboxamide 在 铁粉 、 溶剂黄146 作用下， 以 乙二醇二甲醚 为溶剂， 生成 1-[(2R)-2-[6-[6-(methoxymethyl)pyridin-3-yl]oxy-2-pyridin-2-yl-3H-benzimidazol-5-yl]pyrrolidin-1-yl]ethanone
  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：

  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

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.