N-butyl-4-(methylthio)-3-nitro-4H-chromen-2-amine | 1173429-66-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: N-butyl-4-(methylthio)-3-nitro-4H-chromen-2-amine
• 英文别名: N-butyl-4-(methylthio)-3-nitro-4h-chromen-2-amine；N-butyl-4-methylsulfanyl-3-nitro-4H-chromen-2-amine
• CAS: 1173429-66-7
• 化学式: C₁₄H₁₈N₂O₃S
• 分子量: 294.375
• InChiKey: UWSKPSZSGYAZQW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-butyl-4-(methylthio)-3-nitro-4H-chromen-2-amine 、 对甲苯酰乙腈 在 hydrazine hydrate 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 以81%的产率得到2-(6-(butylamino)-5-nitro-3-(p-tolyl)-4,7-dihydro-1H-pyrazolo[3,4-b]pyridin-4-yl)phenol
  参考文献：
  名称：

  一锅合成重取代的吡唑并[3,4- b ] -4,7-二氢吡啶

  摘要：

  我们已经实现了密集的取代的吡唑并[3,4的组合文库的简便合成b ] -4,7- dihydropyridines- antigenital疣药物鬼臼毒素从5-氨基吡唑和4-（甲硫基）4的模拟物ħ -chromenes 。C（4）吡唑基4 H-色酮，也具有鬼臼毒素的结构特征，是两步一锅缩合反应中的可分离中间体。当将3-氧代-3-苯基丙腈，肼（5-氨基吡唑的前体）和4-（甲硫基）-4 H-色烯在回流的乙醇中加热时，缩合反应以单锅，多组分的方式进行。但是，冷凝在4 H处停止-甲基chrome阶段，其中使用甲基肼或苯肼。我们的发现为鬼臼毒素模拟物的组合文库的合成提供了机会，从而为发现潜在的癌症治疗候选药物铺平了道路。

  DOI：

  10.1021/acscombsci.6b00156
• 作为产物：
  描述：

  N-butyl-N-[(E)-1-(methylsulfanyl)-2-nitro-1-ethenyl]amine 、 水杨醛 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 为溶剂， 反应 18.17h， 以83%的产率得到N-butyl-4-(methylthio)-3-nitro-4H-chromen-2-amine
  参考文献：
  名称：

  Nitroketene acetal chemistry: efficient synthesis of 2-amino-3-nitro-4H-chromenes

  摘要：

  Base-catalyzed reaction of the nitroketene N,S-acetals and the ring substituted 2-hydroxybenzaldehydes afforded a combinatorial library of the 2-alkylamino-3-nitro-4-alkylsulfanyl 4H-chromenes in excellent yields. Nucleophilic displacement of the C4 alkylsulfanyl group with different thiols afforded 4H-chromenes with structural diversity. (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2009.04.018

文献信息

• Synthesis and antimicrobial evaluation of 2-hydroxynaphthalene-1,4-dione and 4H-chromene conjugates
  作者：H. Surya Prakash Rao、Venkata Swamy Tangeti、Lakshmi Narayana Adigopula

  DOI：10.1007/s11164-016-2536-5

  日期：2016.10

  considered to be medicinally privileged scaffolds. We have designed novel conjugates that incorporated both these scaffolds, as such conjugates exhibit unique biological properties reflecting those due to individual units and collective presence. In this work, we have achieved facile, efficient, and high yielding synthesis of 19 such conjugates from readily available 2-alkylamino-4-methylsulfanyl-3-nitro-4H-chromenes

  通常将4 H -Chromene和1,4-萘醌系统视为具有医学特权的支架。我们设计了结合了这两种支架的新型结合物，因为这种结合物表现出独特的生物学特性，反映出由于单个单元和集体存在而产生的生物学特性。在这项工作中，我们已经从容易获得的2-烷基氨基-4-甲基硫烷基-3-硝基-4 H-色烯和2-羟基萘-1,4-二酮中轻松，高效且高收率地合成了19种此类共轭物。高极性nitroketene- Ø，ñ存在于缀合物中的β-乙缩醛单元被设计为防止穿过血脑屏障。我们已经进行了结构活性关系（SAR）研究，该研究基于对三种革兰氏阳性细菌[枯草芽孢杆菌，金 黄色葡萄球菌（MSSA），金黄色葡萄球菌（MRSA）]，一种革兰氏阴性细菌（大肠杆菌）的十种结合物进行初步抗菌筛选的研究）和两种真菌（黑曲霉，白色念珠菌）。SAR研究表明，在4 H的C（6）和C（8）位置具有卤素的共轭物具有C（2）NMe基团的-色烯环显示
• Copper-Catalyzed C(sp³)-C(sp²) Cross-Coupling: Synthesis of 4-Aryl-2-alkyl­amino-3-nitro-4<i>H</i>-chromenes
  作者：H. Surya Prakash Rao、A. Veera Bhadra Rao

  DOI：10.1002/ejoc.201402003

  日期：2014.6

  Inexpensive copper(II) acetate effectively catalyzes cross-coupling of electron-deficient as well as electron-rich arylboronic acids with 4-methylsulfanyl-2-alkylamino-3-nitro-4H-chromenes under near neutral conditions at room temp. to furnish a range of 4-aryl-4H-chromenes. This new strategy enabled substitution of the C(4)SMe group present on a sp3 hybridized carbon of the 4H-chromenes with aryl/heteroaryl

  廉价的醋酸铜 (II) 在室温下近中性条件下有效催化缺电子和富电子芳基硼酸与 4-甲基硫基-2-烷基氨基-3-硝基-4H-色烯的交叉偶联。以提供一系列 4-芳基-4H-色烯。这种新策略使存在于 4H-色烯的 sp3 杂化碳上的 C(4)SMe 基团替换为芳基/杂芳基基团。机理探测表明，CuI-CuIII 循环参与催化。通过 Cu(OAc)2 和 Pd2(dba)3（Suzuki 耦合）催化实现了 C(4)SMe 和 C(6)Br 与芳基的一锅顺序取代。
• Synthesis of 4-(2-hydroxyaryl)-3-nitro-4H-chromenes
  作者：H. Surya Prakash Rao、K. Geetha、M. Kamalraj

  DOI：10.1016/j.tet.2011.08.045

  日期：2011.10

  A combinatorial library of 4-(2-hydroxyaryl)-3-nitro-4H-chromenes was synthesized in high yield by C4-SMe substitution in N-alkyl/phenyl 4-(methylthio)-3-nitro-4H-chromen-2-amines with a variety of phenols. The reaction always provided C2 substitution in the phenol ring, dictated by hydrogen bond interactions between the phenolic hydroxyl group and the nitro group in 3-nitro-4H-chromenes. Reduction of the nitro group with concomitant hydrolysis of the enamine in 4-(2-hydroxyaryl)-3-nitro-4H-chromenes with Zn, Ac(2)O in AcOH furnished hybrid amino-acid lactone incorporating ortho-tyrosine and phenyl alanine moieties. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis, in vitro and in silico antimalarial activity of 7-chloroquinoline and 4H-chromene conjugates
  作者：A. Parthiban、J. Muthukumaran、Ashan Manhas、Kumkum Srivastava、R. Krishna、H. Surya Prakash Rao

  DOI：10.1016/j.bmcl.2015.08.030

  日期：2015.10

  A new series of chloroquinoline-4H-chromene conjugates incorporating piperizine or azipane tethers were synthesized and their anti-malarial activity were evaluated against two Plasmodium falciparum strains namely 3D7 chloroquine sensitive (CQS) and K1 chloroquine resistant (CQR). Chloroquine was used as the standard and also reference for comparison. The conjugates exhibit intense UV absorption with lambda(max) located at 342 nm (log epsilon = 4.0), 254 nm (log epsilon = 4.2), 223 nm (log epsilon = 4.4) which can be used to spectrometrically track the molecules even in trace amounts. Among all the synthetic compounds, two molecules namely 6-nitro and N-piperazine groups incorporated 7d and 6-chloro and N-azapane incorporated 15b chloroquinoline-4H-chromene conjugates showed significant anti-malarial activity against two strains (3D7 and K1) of P. falciparum. These values are lesser than the values of standard antimalarial compound. Molecular docking results suggested that these two compounds showing strong binding affinity with P. falciparum lactate dehydrogenase (PfLDH) and also they occupy the co-factor position which indicated that they could be the potent inhibitors for dreadful disease malaria and specifically attack the glycolytic pathway in parasite for energy production. (C) 2015 Elsevier Ltd. All rights reserved.
• Nitroketene acetal chemistry: efficient synthesis of 2-amino-3-nitro-4H-chromenes
  作者：H. Surya Prakash Rao、K. Geetha

  DOI：10.1016/j.tetlet.2009.04.018

  日期：2009.7

  Base-catalyzed reaction of the nitroketene N,S-acetals and the ring substituted 2-hydroxybenzaldehydes afforded a combinatorial library of the 2-alkylamino-3-nitro-4-alkylsulfanyl 4H-chromenes in excellent yields. Nucleophilic displacement of the C4 alkylsulfanyl group with different thiols afforded 4H-chromenes with structural diversity. (c) 2009 Elsevier Ltd. All rights reserved.