2,8-bis(trifluoromethyl)-4-quinoline carboxaldehyde | 57120-56-6

• 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: 2,8-bis(trifluoromethyl)-4-quinoline carboxaldehyde
• 英文别名: 2,8-bis(trifluoromethyl)-4-quinolinecarboxaldehyde；2,8-bis(trifluoromethyl)quinoline-4-carbaldehyde；2,8-bis-trifluoromethyl-quinoline-4-carbaldehyde；2,8-Bis(trifluormethyl)cinchoninaldehyd
• CAS: 57120-56-6
• 化学式: C₁₂H₅F₆NO
• 分子量: 293.168
• InChiKey: AULJDODYNDIOLA-UHFFFAOYSA-N

物化性质

• 熔点：
  82-84 °C
• 沸点：
  298.7±35.0 °C(Predicted)
• 密度：
  1.499±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2,8-bis(trifluoromethyl)-4-quinoline carboxaldehyde 在 sodium tetrahydroborate 、 cerium(III) chloride 、 Crabtree's catalyst 、 (R,Rp)-1-(2-(diphenylphosphano)ferrocenyl)-1-(2-diphenylphosphanophenyl)-N,N-dimethylmethanamine 、 氢气 、 palladium diacetate 、 戴斯-马丁氧化剂 、 N,N-二甲基苯胺 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 为溶剂， -78.0~130.0 ℃ 、101.33 kPa 条件下， 反应 65.0h， 生成 (S)-tert-butyl 2-((R)-(2,8-bis(trifluoromethyl)quinolin-4-yl)(hydroxy)methyl)piperidine-1-carboxylate
  参考文献：
  名称：

  使用高对映选择性催化硼烷基烯异构化的所有四种甲喹喹立体异构体的简明合成和抗疟活性

  摘要：

  甲氟喹的优缺点：优化了用于抗疟药甲氟喹立体选择性合成的高对映选择性催化硼化异构化/醛烯丙基硼化方法，从而有效合成了所有四种甲氟喹立体异构体和类似物（参见方案）。这些强效化合物的绝对构型是通过化学合成首次确定的。

  DOI：

  10.1002/anie.201303931
• 作为产物：
  描述：

  4-溴-2,8-二(三氟甲基)喹啉 以63%的产率得到
  参考文献：
  名称：

  BLUMBERGS P.; AO M.-S.; LAMONTAGNE M. P.; MARKOVAC A., J. MED. CHEM. , 1975, 18, NO 11, 1122-1126

  摘要：

  DOI：

文献信息

• Asymmetric Total Synthesis of the Antimalarial Drug (+)-Mefloquine Hydrochloride via Chiral <i>N</i>-Amino Cyclic Carbamate Hydrazones
  作者：John D. Knight、Scott J. Sauer、Don M. Coltart

  DOI：10.1021/ol2010193

  日期：2011.6.17

  important antimalarial drug. It is currently manufactured and administered in racemic form; however there are indications regarding the biological activity of the two enantiomers that suggest the superiority of the (+)-form. The asymmetric total synthesis of the (+)-enantiomer of mefloquine hydrochloride is described. The key asymmetric transformation utilized is a novel asymmetric Darzens reaction of

  盐酸甲氟喹是一种重要的抗疟药。目前以消旋形式生产和管理。然而，关于两种对映异构体的生物活性的迹象表明（+）-形式的优越性。描述了盐酸甲氟喹的（+）-对映异构体的不对称全合成。所利用的关键的不对称转化是衍生自N-氨基环状氨基甲酸酯（ACC）手性助剂的手性α-氯-N-氨基环状氨基甲酸酯的新型不对称Darzens反应。
• [EN] ASYMMETRIC ALPHA FUNCTIONALIZATION AND ALPHA, ALPHA BISFUNCTIONALIZATION OF ALDEHYDES AND KETONES<br/>[FR] FONCTIONNALISATION EN ALPHA ET DOUBLE FONCTIONNALISATION EN ALPHA, ALPHA ASYMÉTRIQUES D'ALDÉHYDES ET DE CÉTONES
  申请人：UNIV DUKE

  公开号：WO2009131657A1

  公开（公告）日：2009-10-29

  The present invention relates, generally, to asymmetric α-functionalization and to asymmetric α,α-bisfunctionalization of ketones and aldehydes and, in particular, to chiral auxiliaries suitable for use in effecting such functionalizations and to methods of using same.

  本发明一般涉及不对称α-官能化和不对称α,α-双官能化的酮和醛，特别涉及适用于实现这种官能化的手性辅助剂以及使用相同的方法。
• Diazapane derivatives useful as antagonists of neurokinin 1 receptor and methods for their formation
  申请人：——

  公开号：US20020010174A1

  公开（公告）日：2002-01-24

  The invention relates to compounds of the formula 1 wherein R 1 , R 2 are independently from each other aryl or heteroaryl, wherein the heteroaryl group contains one or two heteroatoms, selected from N, O, or S, and wherein the aryl or heteroaryl groups are optionally substituted by 1 to 3 substituents, which are independently from each other halogen, CF 3 , lower alkoxy or lower alkyl; R 3 is hydrogen, lower alkyl, —(CH 2 ) n N(R) 2 , —(CH 2 ) n -heteroaryl or is a —(CH 2 ) n -non aromatic heterocycle, which heterocycles are optionally substituted by halogen, CF 3 , lower alkoxy or lower alkyl; R 4 is ═O, ═N(CH 2 ) n CH 3 or ═N(CH 2 ) n N(R) 2 ; R 3 and R 4 may be together with the N and C atoms to which they are attached the group —CR 5 ═N—N═; R 5 is hydrogen, —(CH 2 ) n N(R) 2 , —(CH 2 ) n -heteroaryl or is a —(CH 2 ) n -non aromatic heterocycle, which heterocycles are optionally substituted by halogen, CF 3 , lower alkoxy or lower alkyl; R is hydrogen or lower alkyl; n is 0, 1, 2 or 3; and pharmaceutically acceptable acid addition salts and enantiomeric forms thereof. The compounds are useful in the treatment of diseases, related to the NK-1 receptor.

  该发明涉及以下化合物的结构式1，其中R1、R2分别独立地为芳基或杂环芳基，其中杂环芳基含有一个或两个从N、O或S中选择的杂原子，而芳基或杂环芳基可选择地被1至3个取代基取代，这些取代基独立地为卤素、三氟甲基、低烷氧基或低烷基；R3为氢、低烷基、—(CH2)nN(R)2、—(CH2)n-杂环芳基或为—(CH2)n-非芳香杂环，这些杂环可选择地被卤素、三氟甲基、低烷氧基或低烷基取代；R4为HO、N(CH2)nCH3或N(CH2)nN(R)2；R3和R4可以与它们连接的N和C原子一起形成基团—CR5HN—NNH；R5为氢、—(CH2)nN(R)2、—(CH2)n-杂环芳基或为—(CH2)n-非芳香杂环，这些杂环可选择地被卤素、三氟甲基、低烷氧基或低烷基取代；R为氢或低烷基；n为0、1、2或3；以及其药学上可接受的酸盐和对映体形式。这些化合物在治疗与NK-1受体相关的疾病中是有用的。
• 4-quinolinemethanol derivatives as purine receptor antagonists (II)
  申请人：Vernalis Research Limited

  公开号：US06608085B1

  公开（公告）日：2003-08-19

  Use of a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt or prodrug thereof, in the manufacture of a medicament for the treatment or prevention of a disorder in which the blocking of purine receptors, particularly adenosine receptors and more particularly A2a receptors, may be beneficial, such as a movement disorder, for example, Parkinson's Disease or progressive supemuclear palsy, Huntingtons disease, multiple system atrophy, corticobasal degeneration, Wilsons disease, Hallerrorder-Spatz disease, progressive pallidal atrophy, Dopa-responsive dystonia-Parkinsonism, spasticity, Alzheimer's disease or other disorders of the basal ganglia which result in dyskinesias.

  使用以下公式（I）定义的化合物，或其药学上可接受的盐或前药，在制造用于治疗或预防阻断嘌呤受体尤其是腺苷受体，更具体地是A2a受体可能有益的疾病的药物中使用。这些疾病包括运动障碍，例如帕金森病或进行性核上性麻痹，亨廷顿病，多系统萎缩，皮质基底节变性，威尔逊病，霍勒德-斯巴茨病，进行性苍白球萎缩，多巴响应性肌张力障碍-帕金森综合征，痉挛性瘫痪，阿尔茨海默病或其他导致运动失调的基底节疾病。
• Structure–activity relationships amongst 4-position quinoline methanol antimalarials that inhibit the growth of drug sensitive and resistant strains of Plasmodium falciparum
  作者：Erin Milner、William McCalmont、Jayendra Bhonsle、Diana Caridha、Dustin Carroll、Sean Gardner、Lucia Gerena、Montip Gettayacamin、Charlotte Lanteri、ThuLan Luong、Victor Melendez、Jay Moon、Norma Roncal、Jason Sousa、Anchalee Tungtaeng、Peter Wipf、Geoffrey Dow

  DOI：10.1016/j.bmcl.2010.01.001

  日期：2010.2

  Utilizing mefloquine as a scaffold, a next generation quinoline methanol (NGQM) library was constructed to identify early lead compounds that possess biological properties consistent with the target product pro. le for malaria chemoprophylaxis while reducing permeability across the blood-brain barrier. The library of 200 analogs resulted in compounds that inhibit the growth of drug sensitive and resistant strains of Plasmodium falciparum. Herein we report selected chemotypes and the emerging structure activity relationship for this library of quinoline methanols. Published by Elsevier Ltd.