4-<4-<3-(Dibutylamino)phenyl>-4-hydroxypiperidino>-4'-(cyclohexylamino)butyrophenone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-<4-<3-(Dibutylamino)phenyl>-4-hydroxypiperidino>-4'-(cyclohexylamino)butyrophenone
• 英文别名: 4-[4-[3-(Dibutylamino)phenyl]-4-hydroxypiperidino]-4'-(cyclohexylamino)butyrophenone；1-[4-(cyclohexylamino)phenyl]-4-[4-[3-(dibutylamino)phenyl]-4-hydroxypiperidin-1-yl]butan-1-one
• 化学式: C₃₅H₅₃N₃O₂
• 分子量: 547.825
• InChiKey: PGDRQPBJAMXOKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  40
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  55.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  氟哌啶醇 在 potassium carbonate 、 sodium amide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 23.5h， 生成 4-<4-<3-(Dibutylamino)phenyl>-4-hydroxypiperidino>-4'-(cyclohexylamino)butyrophenone
  参考文献：
  名称：

  Nonpeptide HIV Protease Inhibitors. Differential Introduction of Alkylamino Groups into the Two Aryl Rings of Haloperidol

  摘要：

  In efforts to synthesize haloperidol analogues with improved properties as HIV protease inhibitors, methods were sought to introduce mono- and dialkylamino groups into the two aromatic rings of the parent structure. We report here that the reaction of haloperidol with alkylamines in the presence of a strong base (NaNH2) regiospecifically introduces the alkylamino group into the chlorophenyl ring, whereas the same reaction in the presence of a weak base (K2CO3) results in exclusive replacement of the fluorine of the fluorophenyl ring. Different amine functions can be introduced at the two rings by sequential reactions in the presence of, respectively, a strong and a weak base. The reaction catalyzed by NaNH2 involves, at least in part, benzyne formation, whereas the reaction catalyzed by K2CO3 involves direct nucleophilic addition to the aromatic ring. The regiospecificity of the reaction is due to conjugation of the fluorophenyl ring to a ketone group. The fluorophenyl ring is activated by the ketone towards nucleophilic aromatic substitution but is deactivated by the same function when it is converted by strong base to the enolate anion. Carbonyl conjugation of one of two haloaryl groups appears to be a general strategy for regiospecific introduction of alkylamino functions into complex aromatic molecules. The alkylamino derivatives actually prepared are comparable to haloperidol as inhibitors of the HIV-1 protease.

  DOI：

  10.1021/jo00100a021

文献信息

• Nonpeptide HIV Protease Inhibitors. Differential Introduction of Alkylamino Groups into the Two Aryl Rings of Haloperidol
  作者：Kwan Hee Lee、Fiona McPhee、James J. DeVoss、Charles S. Craik、Paul R. Ortiz de Montellano

  DOI：10.1021/jo00100a021

  日期：1994.10

  In efforts to synthesize haloperidol analogues with improved properties as HIV protease inhibitors, methods were sought to introduce mono- and dialkylamino groups into the two aromatic rings of the parent structure. We report here that the reaction of haloperidol with alkylamines in the presence of a strong base (NaNH2) regiospecifically introduces the alkylamino group into the chlorophenyl ring, whereas the same reaction in the presence of a weak base (K2CO3) results in exclusive replacement of the fluorine of the fluorophenyl ring. Different amine functions can be introduced at the two rings by sequential reactions in the presence of, respectively, a strong and a weak base. The reaction catalyzed by NaNH2 involves, at least in part, benzyne formation, whereas the reaction catalyzed by K2CO3 involves direct nucleophilic addition to the aromatic ring. The regiospecificity of the reaction is due to conjugation of the fluorophenyl ring to a ketone group. The fluorophenyl ring is activated by the ketone towards nucleophilic aromatic substitution but is deactivated by the same function when it is converted by strong base to the enolate anion. Carbonyl conjugation of one of two haloaryl groups appears to be a general strategy for regiospecific introduction of alkylamino functions into complex aromatic molecules. The alkylamino derivatives actually prepared are comparable to haloperidol as inhibitors of the HIV-1 protease.