(S)-ethyl 4-(4-(2-(2,8-bis(trifluoromethyl)quinolin-4-yl)-2-hydroxyethyl)piperazin-1-yl)butanoate | 1292282-26-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (S)-ethyl 4-(4-(2-(2,8-bis(trifluoromethyl)quinolin-4-yl)-2-hydroxyethyl)piperazin-1-yl)butanoate
• 英文别名: 4-[(S)-2-Hydroxy-2-[2,8-bis(trifluoromethyl)quinoline-4-yl]ethyl]piperazine-1-butyric acid ethyl ester；ethyl 4-[4-[(2S)-2-[2,8-bis(trifluoromethyl)quinolin-4-yl]-2-hydroxyethyl]piperazin-1-yl]butanoate
• CAS: 1292282-26-8
• 化学式: C₂₃H₂₇F₆N₃O₃
• 分子量: 507.476
• InChiKey: ZPNKEOHCJNJZLB-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  65.9
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  2,8-双(三氟甲基)-4-羟基喹啉 在 potassium osmate(VI) dihydrate 、 四(三苯基膦)钯 、 三甲基氯硅烷 、 AD-mix α 、 potassium carbonate 、 对甲苯磺酸 、 potassium hydroxide 、 三溴氧磷 作用下， 以 甲醇 、 二氯甲烷 、 水 、 异丙醇 、 甲苯 、 叔丁醇 为溶剂， 反应 63.0h， 生成 (S)-ethyl 4-(4-(2-(2,8-bis(trifluoromethyl)quinolin-4-yl)-2-hydroxyethyl)piperazin-1-yl)butanoate
  参考文献：
  名称：

  First enantioselective synthesis of 4-aminoalcohol quinoline derivatives through a regioselective SN2 epoxide opening mechanism

  摘要：

  Mefloquine derivatives, contrary to chloroquine derivatives have not been widely studied to date. Consequently, mefloquine and its derivatives still remain very attractive synthetic targets. Although mefloquine is usually used clinically as a racemic mixture, some studies have shown that its (+)-enantiomer is more potent than the (-)-enantiomer. Moreover, the (-)-enantiomer is responsible for side effects due to reaction with the central nervous system adenosine receptors, while the (+)-enantiomer does no bind at this binding site. Recently, different libraries of racemic 4-aminoalcohol quinolines showed interesting antimalarial activities. Herein, we describe an enantiopure synthetic and straightforward route to prepare pure enantiomer 4-aminoalcohol quinoline derivatives through a 4-oxirane key-intermediate. A regioselective S(N)2 ring opening of this epoxide, by diverse amines, allows us to obtain the corresponding (R) or (S) 4-aminoquinolines with good yields and enantiomeric excesses generally superior to 92%. The reported methodology appears suitable for the synthesis of a large number of pure enantiomer 4-aminoalcohol quinoline derivatives. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2011.01.003

文献信息

• First enantioselective synthesis of 4-aminoalcohol quinoline derivatives through a regioselective SN2 epoxide opening mechanism
  作者：Alexia Jonet、Alexandra Dassonville-Klimpt、Sophie Da Nascimento、Jean-Michel Leger、Jean Guillon、Pascal Sonnet

  DOI：10.1016/j.tetasy.2011.01.003

  日期：2011.1

  Mefloquine derivatives, contrary to chloroquine derivatives have not been widely studied to date. Consequently, mefloquine and its derivatives still remain very attractive synthetic targets. Although mefloquine is usually used clinically as a racemic mixture, some studies have shown that its (+)-enantiomer is more potent than the (-)-enantiomer. Moreover, the (-)-enantiomer is responsible for side effects due to reaction with the central nervous system adenosine receptors, while the (+)-enantiomer does no bind at this binding site. Recently, different libraries of racemic 4-aminoalcohol quinolines showed interesting antimalarial activities. Herein, we describe an enantiopure synthetic and straightforward route to prepare pure enantiomer 4-aminoalcohol quinoline derivatives through a 4-oxirane key-intermediate. A regioselective S(N)2 ring opening of this epoxide, by diverse amines, allows us to obtain the corresponding (R) or (S) 4-aminoquinolines with good yields and enantiomeric excesses generally superior to 92%. The reported methodology appears suitable for the synthesis of a large number of pure enantiomer 4-aminoalcohol quinoline derivatives. (C) 2011 Elsevier Ltd. All rights reserved.