2-(4-chlorophenyl)-4H-pyrido[1,2-a]pyrimidin-4-one | 191218-48-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-(4-chlorophenyl)-4H-pyrido[1,2-a]pyrimidin-4-one
• 英文别名: 2-(4-Chlorophenyl)pyrido[1,2-a]pyrimidin-4-one
• CAS: 191218-48-1
• 化学式: C₁₄H₉ClN₂O
• 分子量: 256.691
• InChiKey: NNVCTRGYNMJAKC-UHFFFAOYSA-N

物化性质

• 熔点：
  203-204 °C(Solv: ethanol (64-17-5); hexane (110-54-3))
• 沸点：
  420.5±55.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(4-chlorophenyl)-4H-pyrido[1,2-a]pyrimidin-4-one 以 paraffin 为溶剂， 反应 2.0h， 生成 2-(4'-Chlorophenyl)-1,8-naphthyridin-4-one
  参考文献：
  名称：

  Antitumor Agents. 174. 2‘,3‘,4‘,5,6,7-Substituted 2-Phenyl-1,8-naphthyridin-4-ones:  Their Synthesis, Cytotoxicity, and Inhibition of Tubulin Polymerization

  摘要：

  Two series of 2',3',4',5,6,7-substituted 8-phenyl-1,8-naphthyridin-4-ones and 2-phenylpyrido-[1,2-a]pyrimidin-4-ones have been synthesized and evaluated as cytotoxic compounds and as inhibitors of tubulin polymerization. Most 2-phenyl-1,8-naphthyridin-4-ones showed potent cytotoxic and antitubulin activities, whereas 2-phenylpyrido[1,2-a]pyrimidin-4-ones showed no activity in either assay. In general, a good correlation was found between cytotoxicity and inhibition of tubulin polymerization in the 2-phenyl-1,8-naphthyridin-4-one series. The 2-phenyl-1,8-naphthyridin-4-ones (44-49) with a methoxy group at the 3'-position showed potent cytotoxicity against most tumor cell lines with GI(50) values in the low micromolar to nanomolar concentration range in the National Cancer Institute's 60 human tumor cell line in vitro screen. Introduction of substituents (e.g. F, Cl, CH3, and OCH3) at the 4'-position led to compounds with reduced or little activity and substitution at the 2'-position resulted in inactive compounds. The effects of various A-ring substitutions on activity depend on the substitution in ring C. Compounds 44-50 were potent inhibitors of tubulin polymerization, with activity nearly comparable to that of the potent antimitotic natural products colchicine, podophyllotoxin, and combretastatin A-4. Compounds 44-49 also inhibited the binding of radiolabeled colchicine to tubulin, but the inhibition was less potent than that obtained with the natural products. Further investigation is underway to determine if substitution at the 3'-position and multisubstitutions in ring C will result in compounds with increased activity.

  DOI：

  10.1021/jm960858s
• 作为产物：
  描述：

  2H-吡啶并[1,2-a]嘧啶-2,4(3H)-二酮 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 1.0h， 生成 2-(4-chlorophenyl)-4H-pyrido[1,2-a]pyrimidin-4-one
  参考文献：
  名称：

  通过Pd催化的烯键式C-O键活化-芳基化反应合成2-芳基吡啶并嘧啶酮，6-芳基尿嘧啶以及三取代和四取代的共轭烯烃

  摘要：

  一种合成重要的生物重要的2-芳基-4 H-吡啶基[1,2- a]的新方法据报道，通过以前未知的Pd催化的吡啶并嘧啶2，4-二酮和巴比妥酸与硼酸的芳基化反应，]嘧啶-4-酮和6-芳基尿嘧啶被芳基化。起始原料容易获得，并且以高收率获得产物。在这种芳基化方法中，还获得了对各种三和四取代的共轭烯酮和链烯酸酯的有效且化学和立体选择的途径。有趣的是，构建这种多样的分子框架的程序是通用的，具有以下特点：出色的底物范围，对各种功能的耐受性，在露天和水性助溶剂中进行反应的异常可行性以及对规模的适应性合成 已发现这是常规/经典路线中的常见限制。该协议以简单的一步高产率途径应用于药学上重要的聚芳基嘧啶嘧啶酮的应用证明了其进一步的合成实用性。

  DOI：

  10.1021/acs.joc.5b00771

文献信息

• Pd-catalyzed carbonylative cycloamidation of ketoimines for the synthesis of pyrido[1,2-a]pyrimidin-4-ones
  作者：Ying Xie、Tengfei Chen、Shaomin Fu、Huanfeng Jiang、Wei Zeng

  DOI：10.1039/c5cc02631h

  日期：——

  The Pd(ii)-catalyzed pyridine-directed carbonylative cycloamidation of ketoimines has provided an efficient protocol for assembly of pyrido[1,2-a]pyrimidin-4-ones.

  Pd（II）催化的吡啶导向羰基环化肼酮的羰基化环酰胺化反应为合成吡啶并[1,2-a]嘧啶-4-酮提供了高效的方案。
• Silver-catalyzed highly efficient synthesis of pyrido[1,2-a]pyrimidin-4-ones from 2-aminopyridines and alkynoates
  作者：Zhengwang Chen、Yuelu Wen、Hao Ding、Guotian Luo、Min Ye、Liangxian Liu、Jun Xue

  DOI：10.1016/j.tetlet.2016.11.079

  日期：2017.1

  heterocycles due to their wide range of bioactivities. An efficient silver-catalyzed intermolecular cyclization of 2-aminopyridines with various alkynoates has been developed. 2-Substituted 4H-pyrido[1,2-a]pyrimidin-4-ones containing a wide range of functional groups are synthesized in the standard conditions. This transformation is conducted under convenient conditions and affords products in good yields

  嘧啶酮由于其广泛的生物活性而成为重要的含氮杂环之一。已经开发了有效的银催化的2-氨基吡啶与各种链烷酸酯的分子间环化。在标准条件下合成含有2-官能取代的4 H-吡啶并[1,2 - a ]嘧啶-4-酮。该转化是在方便的条件下进行的，并以高收率提供产物。
• New efficient approach for the synthesis of 2-alkyl(aryl) substituted 4<i>H</i>-pyrido[1,2-<i>a</i>]pyrimidin-4-ones
  作者：Helio G. Bonacorso、Fernando J. Righi、Isadora R. Rodrigues、Cleber A. Cechinel、Michelle B. Costa、Arci D. Wastowski、Marcos A. P. Martins、Nilo Zanatta

  DOI：10.1002/jhet.5570430136

  日期：2006.1

  A new, efficient and easy route for the preparation of a series of 2-alkyl(aryl) substituted 4-oxo-4H-pyrido-[1,2-a]pyrimidines, where alkyl = CH3; aryl = C6H5, 4-FC6H4, 4-ClC6H4, 4-BrC6H4, 4-CH3C6H4, 4-OCH3C6H4, 4-NO2C6H4 in 45–80 % yield from the reaction of β-alkoxyvinyl trichloromethyl ketones with 2-aminopyridine under mild conditions, is then reported.

  一系列2-烷基（芳基）的制备一种新的，有效的和简单的路线被取代的4-氧代-4- ħ -pyrido- [1,2一]嘧啶类，其中烷基= CH 3 ; 芳= C 6 H ^ 5，4-FC 6 H ^ 4，4-CLC 6 ħ 4，4- BRC 6 ħ 4，4-CH 3 C ^ 6 ħ 4，4-OCH 3 C ^ 6 ħ 4，4-NO 2 C 6高4 据报道，在温和的条件下，β-烷氧基乙烯基三氯甲基酮与2-氨基吡啶的反应收率为45-80％。
• Transition-metal-free lactamization of C(sp³)–H bonds with CO₂: facile generation of pyrido[1,2-<i>a</i>]pyrimidin-4-ones
  作者：Zhen Zhang、Xiao-Yu Zhou、Jin-Gui Wu、Lei Song、Da-Gang Yu

  DOI：10.1039/c9gc03659h

  日期：——

  A novel carbonylation of C(sp3)–H bonds in pyridylamines with one atmosphere of CO2 is reported to synthesize important pyrimidinones in good yields. This transition-metal-free and redox-neutral process features the use of a nontoxic carbonyl source, broad substrate scope, good functional group tolerance, facile scalability and easy product derivatization.

  据报道，吡啶胺中C（sp 3）-H键在一种CO 2气氛下的新型羰基化反应以高收率合成了重要的嘧啶酮。这种无过渡金属和氧化还原中性的方法的特点是使用无毒的羰基来源，广泛的底物范围，良好的官能团耐受性，易扩展性和易于产品衍生化。
• Catalyst‐ and Oxidant‐Free Electrochemical Regioselective Halogenation and Trifluoromethylation of 4<i>H</i>‐Pyrido[1,2‐<i>a</i>]pyrimidin‐4‐ones
  作者：Meiyun Su、Lina Guo、Peiyu Mao、Meng Xiao、Wenjie Liu、Shaohua Wang

  DOI：10.1002/ejoc.202300268

  日期：2023.8

  halogenation and trifluoromethylation of 4H-pyrido[1,2-a]pyrimidin-4-ones with cheap and commercially available sodium salts have been developed under external oxidant-free conditions. The reaction shows broad scope of substrates, high regioselectivity, and good functional group compatibility. Importantly, the electrosynthesis of 4H-pyrido[1,2-a]pyrimidin-4-ones represents a green and advantageous alternative

  已开发出在无外部氧化剂的条件下用廉价且市售的钠盐进行 4 H-吡啶并[1,2- a ]嘧啶-4-酮的无催化剂电化学卤化和三氟甲基化。该反应显示出底物范围广、区域选择性高、官能团相容性好。重要的是，4 H-吡啶并[1,2- a ]嘧啶-4-酮的电合成代表了传统合成方法的绿色且有利的替代方法。