N-((1R)-1-{5-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-3-fluoropyridin-2-yl}ethyl)acetamide | 1160936-54-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N-((1R)-1-{5-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-3-fluoropyridin-2-yl}ethyl)acetamide
• 英文别名: N-((R)-1-{5-[3,5-dichloro-2-(2,2-difluoro-ethoxy)-phenyl]-3-fluoro-pyridin-2-yl}-ethyl)-acetamide；N-[(1R)-1-[5-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-3-fluoropyridin-2-yl]ethyl]acetamide
• CAS: 1160936-54-8
• 化学式: C₁₇H₁₅Cl₂F₃N₂O₂
• 分子量: 407.22
• InChiKey: BGYWSDVAOFPMJJ-MRVPVSSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-((1R)-1-{5-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-3-fluoropyridin-2-yl}ethyl)acetamide 在 盐酸 、 水 作用下， 以 四氢呋喃 为溶剂， 以952%的产率得到((1R)-1-{5-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-3-fluoropyridin-2-yl}ethyl)amine
  参考文献：
  名称：

  Practical Synthesis of a Potent Bradykinin B₁ Antagonist via Enantioselective Hydrogenation of a Pyridyl N-Acyl Enamide

  摘要：

  A practical and efficient synthesis of bradykinin B I antagonist I is described. A convergent strategy was utilized which involved synthesis of three fragments: 3, 6, and 7. Cross coupling of fragments 6 and 7 followed by amidation with 3 enabled efficient synthesis of I in 19 steps total, a 35% overall yield from commercially available pyridine 10. The key to the success of the synthesis was the development of a fluorodenitration step to install the fluorine in pyridine 7 and a catalytic enantioselective hydrogenation of N-acyl enamide 9 to set the stereochemistry.

  DOI：

  10.1021/jo802772d
• 作为产物：
  描述：

  N-[(1R)-1-(5-bromo-3-fluoropyridin-2-yl)ethyl]acetamide 、 [3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]boronic acid 在 potassium phosphate 、 palladium diacetate 、 三苯基膦 作用下， 以 四氢呋喃 、 水 为溶剂， 以96.6%的产率得到N-((1R)-1-{5-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-3-fluoropyridin-2-yl}ethyl)acetamide
  参考文献：
  名称：

  Practical Synthesis of a Potent Bradykinin B₁ Antagonist via Enantioselective Hydrogenation of a Pyridyl N-Acyl Enamide

  摘要：

  A practical and efficient synthesis of bradykinin B I antagonist I is described. A convergent strategy was utilized which involved synthesis of three fragments: 3, 6, and 7. Cross coupling of fragments 6 and 7 followed by amidation with 3 enabled efficient synthesis of I in 19 steps total, a 35% overall yield from commercially available pyridine 10. The key to the success of the synthesis was the development of a fluorodenitration step to install the fluorine in pyridine 7 and a catalytic enantioselective hydrogenation of N-acyl enamide 9 to set the stereochemistry.

  DOI：

  10.1021/jo802772d

文献信息

• [EN] NEW BIARYL AMIDE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS DE BIARYLAMIDE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012089601A1

  公开（公告）日：2012-07-05

  The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12 and A are as described herein, compositions including the compounds and methods of using the compounds.

  这项发明提供了具有通式（I）的新化合物，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12和A如本文所述，包括这些化合物的组合物以及使用这些化合物的方法。
• NEW BIARYL AMIDE DERIVATIVES
  申请人：Aebi Johannes

  公开号：US20120165338A1

  公开（公告）日：2012-06-28

  The invention provides novel compounds having the general formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and A are as described herein, compositions including the compounds and methods of using the compounds.

  这项发明提供了具有一般式（I）的新化合物，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12和A如本文所述，包括这些化合物的组合物以及使用这些化合物的方法。
• Biaryl amide derivatives
  申请人：Aebi Johannes

  公开号：US08912221B2

  公开（公告）日：2014-12-16

  The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12 and A are as described herein, compositions including the compounds and methods of using the compounds.

  本发明提供了一种具有一般式(I)的新化合物，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12和A如本文所述，包括该化合物的组合物和使用该化合物的方法。
• US8912221B2
  申请人：——

  公开号：US8912221B2

  公开（公告）日：2014-12-16
• Practical Synthesis of a Potent Bradykinin B₁ Antagonist via Enantioselective Hydrogenation of a Pyridyl <i>N</i>-Acyl Enamide
  作者：Paul D. O’Shea、Danny Gauvreau、Francis Gosselin、Greg Hughes、Christian Nadeau、Amélie Roy、C. Scott Shultz

  DOI：10.1021/jo802772d

  日期：2009.6.19

  A practical and efficient synthesis of bradykinin B I antagonist I is described. A convergent strategy was utilized which involved synthesis of three fragments: 3, 6, and 7. Cross coupling of fragments 6 and 7 followed by amidation with 3 enabled efficient synthesis of I in 19 steps total, a 35% overall yield from commercially available pyridine 10. The key to the success of the synthesis was the development of a fluorodenitration step to install the fluorine in pyridine 7 and a catalytic enantioselective hydrogenation of N-acyl enamide 9 to set the stereochemistry.