(S)-1-(2,8-bis(trifluoromethyl)quinolin-4-yl)-2-(pentylamino)ethanol | 1292282-27-9

• 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)-1-(2,8-bis(trifluoromethyl)quinolin-4-yl)-2-(pentylamino)ethanol
• 英文别名: (1S)-1-[2,8-bis(trifluoromethyl)-4-quinolyl]-2-(pentylamino)ethanol；(1S)-1-[2,8-bis(trifluoromethyl)quinolin-4-yl]-2-(pentylamino)ethanol
• CAS: 1292282-27-9
• 化学式: C₁₈H₂₀F₆N₂O
• 分子量: 394.36
• InChiKey: ZUNMBCXPZDPUJT-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  45.2
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2,8-双(三氟甲基)-4-羟基喹啉 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium osmate(VI) dihydrate 、 三甲基氯硅烷 、 AD-mix α 、 四丁基溴化铵 、 potassium carbonate 、 对甲苯磺酸 、 三溴氧磷 作用下， 以 甲醇 、 二氯甲烷 、 水 、 异丙醇 、 乙腈 、 叔丁醇 为溶剂， 反应 43.0h， 生成 (S)-1-(2,8-bis(trifluoromethyl)quinolin-4-yl)-2-(pentylamino)ethanol
  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

• Enantioselective synthesis method of 4-aminoalcoholquinoline derivatives and the use
  申请人：Université de Picardie Jules Verne

  公开号：EP2487157A1

  公开（公告）日：2012-08-15

  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 racemate 4-aminoalcoholquinolines showed interesting anti-malarial activities. Herein, the present invention describes an enantiopure synthetic and straightforward route to prepare pure enantiomer 4-aminoalcoholquinoline derivatives through the 4-oxirane key-intermediate. A regioselective SN2 ring opening of this epoxide, by diverse amines, allows 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-aminoalcoholquinoline derivatives.

  梅氟喹诺酮衍生物与氯喹诺酮衍生物相比，迄今为止尚未广泛研究。因此，梅氟喹诺酮及其衍生物仍然是非常有吸引力的合成目标。虽然梅氟喹诺酮通常作为外消旋混合物在临床上使用，但一些研究表明其（+）-对映体比（-）-对映体更有效。此外，（-）-对映体由于与中枢神经系统腺苷受体的反应而导致副作用，而（+）-对映体则不会在该结合位点结合。最近，不同的外消旋4-氨基醇喹啉库显示出有趣的抗疟活性。在此，本发明描述了一种对映纯的合成和直接的途径，通过4-环氧丙烷关键中间体制备纯对映体4-氨基醇喹啉衍生物。通过多种胺的区域选择性SN2环开放该环氧化物，可以获得相应的（R）或（S）4-氨基喹啉，并且收率和对映体过量通常高于92％。所报告的方法适用于合成大量对映纯的4-氨基醇喹啉衍生物。
• [EN] 4-AMINOALCOHOLQUINOLINE DERIVATIVES, ENANTIOSELECTIVE SYNTHESIS METHODS AND THE USE THEREOF<br/>[FR] DÉRIVÉS DE 4-AMINO-ALCOOLQUINOLÉINE, PROCÉDÉS DE SYNTHÈSE ÉNANTIOSÉLECTIVE ET UTILISATION DE CEUX-CI
  申请人：UNIV PICARDIE

  公开号：WO2012107532A1

  公开（公告）日：2012-08-16

  The present invention is intended to provide new antimalarial compounds with a strong antimalarial activity as well as antibacterial activity with few neurological side effects and a new enantioselective pathway to mefloquine amino-analogs allowing the access of such compounds. The present invention relates to new 4 -aminoalcohol quinoline derivatives of formula (I), as well as the synthesis methods and the uses of such derivatives. In which Y is one selected from formulae (II) to (III). In which Z is selected from formulae (IV) to (VI), and wherein R1, R2, R3, R4, R5, R6, R7 and n are as defined in the claims.

  本发明旨在提供具有强抗疟活性和抗菌活性，且神经系统副作用少的新型抗疟疾化合物，以及一种新的对映选择性途径，允许访问这种化合物的甲氟喹胺类似物。本发明涉及公式(I)的新型4-氨基醇喹啉衍生物，以及这种衍生物的合成方法和用途，其中Y是从公式(II)到(III)中选择的一个，Z是从公式(IV)到(VI)中选择的一个，R1、R2、R3、R4、R5、R6、R7和n如权利要求所定义。
• 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.