2-氯-4-甲基-6-硝基喹啉 | 54965-59-2

• 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
• 中文名称: 2-氯-4-甲基-6-硝基喹啉
• 中文别名: 2-氯-4-甲基-六硝基癸啉；2-氯-4-甲基-六硝基喹啉；喹啉,2-氯-4-甲基-6-硝基-
• 英文名称: 2-chloro-4-methyl-6-nitroquinoline
• CAS: 54965-59-2
• 化学式: C₁₀H₇ClN₂O₂
• mdl: MFCD00169016
• 分子量: 222.631
• InChiKey: PTZXWOQFSDHSDM-UHFFFAOYSA-N

物化性质

• 熔点：
  212-213 °C
• 沸点：
  382.7±37.0 °C(Predicted)
• 密度：
  1.419±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  58.7
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933499090

反应信息

• 作为反应物：
  描述：

  2-氯-4-甲基-6-硝基喹啉 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 48.0h， 生成 4-methyl-2-(4-methylpiperazin-1-yl)quinolin-6-ylamine
  参考文献：
  名称：

  Identification and optimization of novel 6-acylamino-2-aminoquinolines as potent Hsp90 C-terminal inhibitors

  摘要：

  In order to discover novel Hsp90 inhibitors targeting the C-terminal ATP binding pocket, a novobiocin derivative based ROCS model was constructed for virtual screening. Compound 13 was identified as the lead compound and then systematical structure activity relationship (SAR) study was conducted. These efforts led to compound 69, which exhibited potent anti-proliferative activities against MCF7 and SKBr3 breast cancer cell lines. In 4T1 mice breast cancer models, 69 exhibited potent tumor growth inhibition and anti-metastasis effect. Compound 69 as a potent antitumor agent targeting the Hsp90 C-terminal is worthy of further pre-clinical study. (C) 2017 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2017.07.080
• 作为产物：
  描述：

  乙酰乙酰对硝基苯胺 在 硫酸 、 三氯氧磷 作用下， 生成 2-氯-4-甲基-6-硝基喹啉
  参考文献：
  名称：

  CCCIII.—4-甲基-，4：6-，4：7-和4：8-二甲基-2-羟基喹啉的衍生物

  摘要：

  DOI：

  10.1039/jr9300002346

文献信息

• Novel 8-nitroquinolin-2(1H)-ones as NTR-bioactivated antikinetoplastid molecules: Synthesis, electrochemical and SAR study
  作者：Julien Pedron、Clotilde Boudot、Sébastien Hutter、Sandra Bourgeade-Delmas、Jean-Luc Stigliani、Alix Sournia-Saquet、Alain Moreau、Elisa Boutet-Robinet、Lucie Paloque、Emmanuelle Mothes、Michèle Laget、Laure Vendier、Geneviève Pratviel、Susan Wyllie、Alan Fairlamb、Nadine Azas、Bertrand Courtioux、Alexis Valentin、Pierre Verhaeghe

  DOI：10.1016/j.ejmech.2018.06.001

  日期：2018.7

  important shift of the redox potential (+0.3 V in comparison with 8-nitroquinoline). With the assistance of computational chemistry, a set of derivatives presenting a large range of redox potentials (from −1.1 to −0.45 V) was designed and provided a list of suitable molecules to be synthesized and tested. This approach highlighted that, in this series, only substrates with a redox potential above −0.6 V

  为了研究抗寄生虫8-硝基喹啉-2（1 H）-一药效基团，以1-5个步骤合成了一系列31种衍生物，并在体外针对婴儿利什曼原虫和布鲁氏锥虫进行了评估。。并行地，通过循环伏安法测量所有分子的还原电势。构效关系首先表明，抗菌活性取决于内酰胺官能团与硝基之间的分子内氢键（通过X射线衍射描述），这是氧化还原电势（+0.3 V与氧化还原电势相比重要的变化）的重要原因。 8-硝基喹啉）。在计算化学的帮助下，设计了一组表现出大范围氧化还原电势（从-1.1至-0.45 V）的衍生物，并提供了一系列适合合成和测试的分子。该方法强调了在该系列中，只有氧化还原电势高于-0.6 V的底物才对婴儿乳杆菌具有活性。。然而，在T中未观察到氧化还原电势与体外抗寄生虫活性之间的这种关系。b。布鲁西。化合物22是该系列中的一种新型命中化合物，对人类HepG2细胞系既显示出抗疟原虫活性又具有抗锥虫活性，并且具有较低的细胞毒性。化合物22被L
• [EN] SUBSTITUTED QUINOLINES AS MCR MODULATORS<br/>[FR] QUINOLEINES SUBSTITUEES, UTILISEES COMME MODULATEURS DE LA MCH
  申请人：ARGENTA DISCOVERY LTD

  公开号：WO2005035521A1

  公开（公告）日：2005-04-21

  Quinolines of formula (I) are useful as MCH mediators, and in the therapy of obesity.

  式(I)的喹啉在MCH介质和肥胖治疗中很有用。
• Novel Synthesis of 2-Chloroquinolines from 2-Vinylanilines in Nitrile Solvent
  作者：Byoung Se Lee、Jae Hak Lee、Dae Yoon Chi

  DOI：10.1021/jo016196i

  日期：2002.11.1

  2-Vinyl- or heteroaryl-substituted anilines were reacted with diphosgene in acetonitrile solution via a reactive imidoyl moiety to afford the corresponding 2-chloroquinolines. Facile syntheses of nine 2-chloroquinoline derivatives from several anilines and their postulate mechanism is described. The postulate mechanism of 2-chloroquinoline formation via imidoyl moiety as a good leaving group shows

  使2-乙烯基-或杂芳基取代的苯胺与二光气在乙腈溶液中经由反应性亚胺基部分反应，得到相应的2-氯喹啉。描述了几种苯胺的九种2-氯喹啉衍生物的简便合成及其推定机理。通过亚氨基基团作为良好的离去基团形成2-氯喹啉的推测机理表明，该反应由以下三个步骤组成：（1）生成异氰酸苯酯；（2）喹啉环的形成；（3）在C2位的氯化喹啉。
• Photolytic ring-expansions of 6-azidoquinolines and 6-azidodiazines: some unexpected azepine ring-opening reactions
  作者：Roy Hayes、Joseph M. Schofield、Robert K. Smalley、David I.C. Scopes

  DOI：10.1016/s0040-4020(01)89775-1

  日期：1990.1

  Photolysis of 6-azidoquianazoline in MeOH-KOMe-dioxan yields 8,9-dihydro-5,7-dimethoxy-5H-pyrimido[5,4-]azepine (5) which on acid hydrolysis ring-opens to the pyrimidine-carbaldehyde (7). The mechanism of formation of this unexpected dimethoxypyrimido-azepine is discussed and related to previous similar results involving 6-azido-2,3-dihydrofuro- and 6-azido-23-dihydrothieno-[2,3-b]quinolines

  6-叠氮喹啉在MeOH-KOMe-二恶烷中的光解产生8,9-二氢-5,7-二甲氧基-5H-嘧啶并[5,4-]氮杂（5），在酸水解时开环反应成嘧啶-甲醛（ 7）。讨论了这种意外的二甲氧基嘧啶基-氮杂a的形成机理，并与先前涉及6-叠氮基-2,3-二氢呋喃基和6-叠氮基-23-二氢噻吩基-[2,3-b]喹啉的类似结果相关联
• Quaternary salts of pyrimidylaminoquinolines
  申请人：ICI LTD

  公开号：US02585905A1

  公开（公告）日：1952-02-19

  Mono- and di-quaternary salts of pyrimidylaminoquinolines, possessing trypanocidal activity and of the general formula Pq-NH-A, (wherein P represents a 2-, 4- (or 6-) amino-substituted pyrimidine nucleus which is attached to the -NH- linkage at another of the 2-, 4- (or 6-) positions and which may be further substituted in the remaining 2-, 4- (or 6-) position by an alkyl radical of not more than 5 carbon atoms or an amino group, A represents Q or Qq where Q is a quinoline nucleus which is substituted in the 2- or 4- position by an amino group and may be further substituted by an alkyl group of not more than 5 carbon atoms, and which bears the linking-NH- group in the 6-position, and the symbols q indicate that the preceding nuclei P and Q respectively are in the form of their quaternary salts), or tantomeric forms thereof, are manufactured by reacting a compound of the formula PqX (wherein X represents a halogen atom or a group -SR, R being a hydrocarbon radical, obtainable by the process of Specification 634,471) with a compound of the formula NH2A, or a salt thereof, or a substance which will give rise thereto under the reaction conditions (e.g. an acyl derivative thereof). The reaction may be effected by heating the reactants together, advantageously in a liquid medium and in the presence of an acid. In examples: (1) 2 - chloro - 4 - methyl - 6 - aminopyrimidine 3-methiodide is boiled with 4 : 6-diaminoquinaldine methochloride in dilute hydrochloric acid to produce 4-amino-6-(61-amino - 41 - methylpyrimidyl - 21 - amino) - quinaldine 1 : 31-dimethiodide; (2) 4-chloro-2-amino-6-methylpyrimidine 1-methiodide is boiled in water with 4 : 6-diaminoquinaldine methochloride hydrochloride, yielding 4-amino-6-(21-amino-61-methylpyrimidyl-41-amino) p -quinaldine 1 : 11-dimethiodide, or the tantomeric 4-amino-6-(21-imino-11 : 61-dimethyl-11 : 21-dihydropyrimidyl-41-amino)-quinaldine 1-methiodide hydriodide or 4-imino-1-methyl-6-(21-amino-61-methylpyrimidyl -41-amino)-1 : 4-dihydroquinaldine 11-methiodide hydriodide or 4-imino-1-methyl-6-(21-imino-11 : 61-dimethyldihydropyrimidyl-41-amino)-1 : 4-dihydroquinaldine dihydriodide; the product may be converted into the dimethochloride by treating an aqueous solution thereof with hydrochloric acid or sodium chloride, or into the dimethobromide by analogous treatment; (3) the pyrimidine reactant in (2) is replaced by 4-iodo-2-amino-6-methylpyrimidine 3-methiodide, producing the corresponding 1 : 31-dimethiodide, which may be converted with silver chloride into the dimethochloride and with sodium carbonate solution into 4-amino-6-(21-imino-31 : 61-dimethyl-2 : 3-dihydropyrimidyl-41-amino)-quinaldine 1-methiodide; (4) 4 : 6-diaminoquinaldine methochloride is heated with 2-amino-4-methylthio6-methylpyrimidine 1-methiodide to give the product of (2); (5) the quinaldine reactant in (3) is replaced by 4 : 6-diaminoquinaldine methiodide; (6) the pyrimidine reactant in (5) is replaced by 4-chloro-2 : 6-diaminopyrimidine 3-methiodide, and (7) by the corresponding 1-methiodide; (8) 4 : 6-diaminoquinoline methiodide is reacted as in (2); (9) the quinaldine reactant of (2) is replaced by 2 : 6-diaminolepidine methiodide; (10) 4-amino-6-acetylaminoquinaldine 1-metho-methylsulphate and 4-chloro-2-amino-6-methylpyrimidine 1-methomethylsulphate are reacted as in (1) and the product is treated with hydrochloric acid to give the dimethochloride of (2); (11) the pyrimidine reactant of (10) is replaced by the 1-methiodide; (12) 4 : 6-diaminoquinaldine and 4-chloro-2 : 6-diaminopyrimidine 3-methiodide are reacted as in (1) to produce 4-amino-6-(21 : 61-diaminopyrimidyl-41-amino)-quinaldine 31-methiodide hydriodide; (13) 4 : 6 - diaminoquinaldine ethiodide is reacted as in (2). Specification 634,531 also is referred to. 4 : 6-Diaminoquinaldinium salts.-The methochloride hydrochloride is obtainable by treating 4-amino-6-acetylaminoquinaldine with dimethyl sulphate in nitrobenzene and refluxing the product with aqueous hydrochloric acid. It may be converted into the methochloride by the action of sodium carbonate solution and into the methiodide by the action of a solution of sodium carbonate and excess of potassium iodide. The ethiodide is obtainable by treating 4-amino-6-acetylaminoquinaldine with diethyl sulphate in nitrobenzene, treating the product with sodium iodide solution, hydrolysing with hydrochloric acid and adding sodium carbonate and sodium iodide. 4 : 6-Diaminoquinoline methiodide is obtainable from ethyl 6-acetylamino-4-hydroxyquinoline-2-carboxylate by saponification, decarboxylation, treatment with phosphorous oxychloride and then with ammonia in the presence of phenol, quaternation of the resulting 4-amino-6-acetylaminoquinoline by means of dimethyl sulphate in nitrobenzene, hydrolysis with hydrochloric acid and treatment with sodium carbonate and sodium iodide. 2 : 6-Diaminolepidine methiodide is obtainable from 2-chloro-6-nitrolepidine by treatment with ammonia in the presence of phenol and acetamide, quaternation with dimethyl sulphate in nitrobenzene, treatment with excess of sodium chloride, reduction of the nitro group with iron and methanolic hydrochloric acid and treatment with sodium carbonate and sodium iodide.

  具有抗锥虫活性的嘧啶基氨基喹啉的单、双季铵盐，其一般式为Pq-NH-A（其中P代表2-、4-（或6-）氨基取代的嘧啶核，该核附着在另一个2-、4-（或6-）位置的-NH-连接处，并且在其余的2-、4-（或6-）位置上可能进一步取代为不超过5个碳原子的烷基或氨基，A代表Q或Qq，其中Q是一个喹啉核，在2-或4-位置上被氨基取代，并且可能进一步被不超过5个碳原子的烷基取代，其在6-位置带有连接-NH-基团，符号q表示前面的核P和Q分别以其季铵盐的形式存在，或其异构体，可以通过将公式PqX（其中X代表卤素原子或由规范634,471的过程获得的-SR基团，其中R是一个碳氢基团）与公式NH2A或其盐或在反应条件下将产生该物质的物质（例如，其酰基衍生物）反应制备。反应可以通过加热反应物一起进行，优选在液体介质中，在酸的存在下进行。在例子中：（1）2-氯-4-甲基-6-氨基嘧啶3-碘化物在稀盐酸中与4：6-二氨基喹啉甲基氯化物沸腾，产生4-氨基-6-（6-氨基-4-甲基嘧啶-2-氨基）-喹啉1：3-二碘化物；（2）4-氯-2-氨基-6-甲基嘧啶1-碘甲烷酸盐在水中与4：6-二氨基喹啉甲基氯化物盐酸盐沸腾，产生4-氨基-6-（2-氨基-6-甲基嘧啶-4-氨基）-喹啉1：1-二碘化物，或其异构体4-氨基-6-（2-亚氨基-1，1：6，1-二甲基-2，3-二氢嘧啶-4-氨基）-喹啉1-碘甲烷酸盐，或4-亚氨基-1-甲基-6-（2-氨基-6-甲基嘧啶-4-氨基）-1：4-二氢喹啉11-碘甲烷酸盐，或4-亚氨基-1-甲基-6-（2-亚氨基-1，1：6，1-二甲基嘧啶-4-氨基）-1：4-二氢喹啉二碘化物；可以通过用盐酸或氯化钠处理其水溶液将产物转化为二甲基氯化物或类似处理将其转化为二甲基溴化物；（3）（2）中的嘧啶反应物被4-碘-2-氨基-6-甲基嘧啶3-碘甲烷酸盐所取代，产生相应的1：3-二碘化物，该化合物可以与氯化银转化为二甲基氯化物，或与碳酸钠溶液转化为4-氨基-6-（2-亚氨基-3,1：6,1-二甲基嘧啶-4-氨基）-喹啉1-碘甲烷酸盐；（4）4：6-二氨基喹啉甲基氯化物与2-氨基-4-甲硫基-6-甲基嘧啶1-碘甲烷酸盐加热，产生（2）的产物；（5）（3）中的喹啉反应物被4：6-二氨基喹啉甲烷酸盐所取代；（6）（5）中的嘧啶反应物被4-氯-2：6-二氨基嘧啶3-碘甲烷酸盐所取代，（7）被相应的1-碘甲烷酸盐所取代；（8）4：6-二氨基喹啉甲烷酸盐如（2）中所述反应；（9）（2）中的喹啉反应物被2：6-二氨基乙二噻啶甲烷酸盐所取代；（10）4-氨基-6-乙酰氨基喹啉1-甲硫酸盐和4-氯-2-氨基-6-甲基嘧啶1-甲硫酸盐如（1）中所述反应，产物用盐酸处理后得到（2）的二甲基氯化物；（11）（10）中的嘧啶反应物被1-甲烷基碘化物所取代；（12）4：6-二氨基喹啉和4-氯-2：6-二氨基嘧啶3-碘甲烷酸盐如（1）中所述反应，产生4-氨基-6-（2：4-二氨基嘧啶-6,1-二氨基）-喹啉3-碘甲烷酸盐；（13）4：6-二氨基喹啉乙碘化物如（2）中所述反应。规范634,531也被提到。4：6-二氨基喹啉盐-甲基氯化物盐酸盐可以通过将4-氨基-6-乙酰氨基喹啉与硫酸二甲酯在硝基苯中处理，并将产物与水合盐酸回流处理得到。它可以通过钠碳酸溶液的作用转化为甲基氯化物，通过钠碘化物溶液和过量的碘化钾的作用转化为甲基碘化物。乙碘化物可以通过将4-氨基-6-乙酰氨基喹啉与硫酸二乙酯在硝基苯中处理，用碘化钠溶液处理产物，水解并加入碳酸钠和碘化钠得到。4：6-二氨基喹啉甲烷酸盐可以通过将乙基6-乙酰氨基-4-羟基喹啉-2-羧酸酯皂化、脱羧、用氯化亚磷酰处理，然后在苯酚存在下与氨一起处理，用硝基苯中的二甲基硫酸盐季铵化得到4-氨基-6-乙酰氨基喹啉，用盐酸水解并用碳酸钠和碘化钠处理得到。2：6-二氨基乙二噻啶甲烷酸盐可以通过用苯酚和乙酰胺处理2-氯-6-硝基乙二噻啶，用硝基苯中的二甲基硫酸盐季铵化，过量的氯化钠处理，铁和甲醇盐酸还原硝基基团，然后用碳酸钠和碘化钠处理得到。