2-(4-(trifluoromethyl)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one | 1335239-79-6

• 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-(trifluoromethyl)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one
• 英文别名: 2-[4-(Trifluoromethyl)phenyl]pyrido[1,2-a]pyrimidin-4-one
• CAS: 1335239-79-6
• 化学式: C₁₅H₉F₃N₂O
• 分子量: 290.244
• InChiKey: ORIXLUQZGSJBAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 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-(trifluoromethyl)phenyl)-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

• Manganese‐Catalyzed Carbonylative Annulations for Redox‐Neutral Late‐Stage Diversification
  作者：Yu‐Feng Liang、Ralf Steinbock、Annika Münch、Dietmar Stalke、Lutz Ackermann

  DOI：10.1002/anie.201801111

  日期：2018.5.4

  inexpensive, nontoxic manganese catalyst enabled unprecedented redox‐neutral carbonylative annulations under ambient pressure. The manganese catalyst outperformed all other typically used base and precious‐metal catalysts. The outstanding versatility of the manganese catalysis manifold was reflected by ample substrate scope, setting the stage for effective late‐stage manipulations under racemization‐free

  廉价，无毒的锰催化剂可在环境压力下实现前所未有的氧化还原中性羰基环化反应。锰催化剂的性能优于所有其他常用的碱金属和贵金属催化剂。充足的底物范围反映了锰催化歧管出色的多功能性，为在无消旋条件下对许多市售药物和天然产物（包括生物碱，氨基酸，类固醇和碳水化合物）进行有效的后期操作奠定了基础。
• Suzuki–Miyaura cross-coupling reactions of halo derivatives of 4H-pyrido[1,2-a]pyrimidin-4-ones
  作者：Annamária Molnár、Anita Kapros、László Párkányi、Zoltán Mucsi、Gábor Vlád、István Hermecz

  DOI：10.1039/c1ob05505d

  日期：——

  cross-coupling reactions of halo derivatives of 4H-pyrido[1,2-a]pyrimidin-4-one with (het)arylboronic acids allow easy access to (het)aryl and vinyl derivatives of this bicycle in good to excellent yields, even from chloro derivatives. The sequence of reactivity of the halogen in the different positions of the ring system was also investigated. 6-Phenyl-4H-pyrido[1,2-a]pyrimidin-4-one could be prepared by thermal

  钯催化的卤素衍生物的Suzuki-Miyaura交叉偶联反应 4 H-吡啶并[1,2- a ]嘧啶-4-一与（杂）芳基硼酸一起使用，即使从氯代衍生物中也可以很容易地获得该自行车的（杂）芳基和乙烯基衍生物。还研究了卤素在环系统不同位置的反应顺序。6-苯基-4 H-吡啶并[1,2- a ]嘧啶-4-一 可以通过热环化制备 异亚丙基（6-苯基吡啶-2-基氨基）亚甲基丙二酸酯，以及少量的7-苯基-1,4-二氢-1,8-萘啶-4-酮。
• 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。
• CuI-catalyzed synthesis of multisubstituted pyrido[1,2-<i>a</i>]pyrimidin-4-ones through tandem Ullmann-type C–N cross-coupling and intramolecular amidation reaction
  作者：Baichuan Mo、Chunxia Chen、Jinsong Peng

  DOI：10.1039/d3ra04454h

  日期：——

  2-a]pyrimidin-4-ones were synthesized via a one-pot tandem CuI-catalyzed C–N bond formation/intramolecular amidation reaction at 130 °C in DMF. This protocol features simple operation, broad substrate scope, good functional group tolerance and gram scale preparation, thus allowing practical and modular synthesis of pyrido[1,2-a]pyrimidin-4-ones from readily available 2-halopyridine and (Z)-3-amino-3-arylacrylate

  通过一锅串联 CuI 催化 C-N 键形成/分子内酰胺化反应在 130 °C DMF 中合成各种多取代吡啶并[1,2- a ]嘧啶-4-酮。该方案具有操作简单、底物范围广、官能团耐受性好和克级制备的特点，从而可以从容易获得的2-卤代吡啶和( Z )-吡啶并[1,2- a ]嘧啶-4-酮进行实用和模块化合成。 3-氨基-3-芳基丙烯酸酯的产率良好至优异。
• Scaffold-hopping of bioactive flavonoids: Discovery of aryl-pyridopyrimidinones as potent anticancer agents that inhibit catalytic role of topoisomerase IIα
  作者：Garima Priyadarshani、Suyog Amrutkar、Anmada Nayak、Uttam C. Banerjee、Chanakya N. Kundu、Sankar K. Guchhait

  DOI：10.1016/j.ejmech.2016.06.024

  日期：2016.10

  A strategy of scaffold-hopping of bioactive natural products, flavones and isofl avones, leading to target-based discovery of potent anticancer agents has been reported for the first time. Scaffold-hopped flavones, 2-aryl-4H-pyrido[1,2-a]pyrimidin-4-ones and the scaffold-hopped isofiavones, 3-aryl-pyrido[1,2-a]pyrimidin-4-ones were synthesized via Pd-catalyzed activation-arylation methods. Most of the compounds were found to exhibit pronounced human topoisomerase II alpha (hTopoll alpha) inhibitory activities and several compounds were found to be more potent than etoposide (a hTopoll alpha-inhibiting anticancer drug). These classes of compounds were found to be hTopoll alpha-selective catalytic inhibitors while not interfering with topoisomerase I and interacted with DNA plausibly in groove domain. Cytotoxicities against various cancer cells, low toxicity in normal cells, and apoptotic effects were observed. Interestingly, compared to parent flavones/isoflavones, their scaffold-hopped analogs bearing alike functionalities showed significant/enhanced hTopoII alpha-inhibitory and cytotoxic properties, indicating the importance of a natural product-based scaffold-hopping strategy in the drug discovery. (C) 2016 Elsevier Masson SAS. All rights reserved.