N-(3-(4-(2,3-dichlorophenyl)piperazin-1-yl)-4-fluorobutyl)benzofuran-2-carboxamide | 1584154-98-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-(3-(4-(2,3-dichlorophenyl)piperazin-1-yl)-4-fluorobutyl)benzofuran-2-carboxamide
• 英文别名: N-[3-[4-(2,3-dichlorophenyl)piperazin-1-yl]-4-fluorobutyl]-1-benzofuran-2-carboxamide
• CAS: 1584154-98-2
• 化学式: C₂₃H₂₄Cl₂FN₃O₂
• 分子量: 464.367
• InChiKey: QBRAQPXCJIBXIU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  48.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3-hydroxybutyl)isoindoline-1,3-dione 在 氯化亚砜 、 二乙胺基三氟化硫 、 肼 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 18.0h， 生成 N-(3-(4-(2,3-dichlorophenyl)piperazin-1-yl)-4-fluorobutyl)benzofuran-2-carboxamide
  参考文献：
  名称：

  Chiral Resolution and Serendipitous Fluorination Reaction for the Selective Dopamine D3 Receptor Antagonist BAK2-66

  摘要：

  The improved chiral synthesis of the selective dopamine D3 receptor (D3R) antagonist (R)-N-(4-(4-(2,3-dichlorophenyl)piperazin- I -yl) -3-hydroxybutyl)1H-indole-2carboxamide ((R)-PG648) is described. The same chiral secondary alcohol intermediate was used to prepare the enantiomers of a 3-F-benzofuranyl analogue, BAK 2-66. The absolute configurations of the 3-F enantiomers were assigned from their X-ray crystal structures that confirmed retention of configuration during fluorination with N,N-diethylaminosulfur trifluoride (DAST). (R)-BAK2-66 showed higher D3R affinity and selectivity than its (S)-enantiomer; however, it had lower D3R affinity and enantioselectivity than (R)-PG648. Further, importance of the 4-atom linker length between the aryl amide and 4-phenylpiperazine was demonstrated with the 4-fluorobutylproduct (8).

  DOI：

  10.1021/ml500006v

文献信息

• Chiral Resolution and Serendipitous Fluorination Reaction for the Selective Dopamine D3 Receptor Antagonist BAK2-66
  作者：Vivek Kumar、Ashwini K. Banala、Erick G. Garcia、Jianjing Cao、Thomas M. Keck、Alessandro Bonifazi、Jeffery R. Deschamps、Amy Hauck Newman

  DOI：10.1021/ml500006v

  日期：2014.6.12

  The improved chiral synthesis of the selective dopamine D3 receptor (D3R) antagonist (R)-N-(4-(4-(2,3-dichlorophenyl)piperazin- I -yl) -3-hydroxybutyl)1H-indole-2carboxamide ((R)-PG648) is described. The same chiral secondary alcohol intermediate was used to prepare the enantiomers of a 3-F-benzofuranyl analogue, BAK 2-66. The absolute configurations of the 3-F enantiomers were assigned from their X-ray crystal structures that confirmed retention of configuration during fluorination with N,N-diethylaminosulfur trifluoride (DAST). (R)-BAK2-66 showed higher D3R affinity and selectivity than its (S)-enantiomer; however, it had lower D3R affinity and enantioselectivity than (R)-PG648. Further, importance of the 4-atom linker length between the aryl amide and 4-phenylpiperazine was demonstrated with the 4-fluorobutylproduct (8).