7-甲基-4H-吡啶并[1,2-A]嘧啶-4-酮 | 23443-20-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 中文名称: 7-甲基-4H-吡啶并[1,2-A]嘧啶-4-酮
• 英文名称: 7-methyl-4H-pyrido[1,2-a]pyrimidin-4-one
• 英文别名: 7-methylpyrido[1,2-a]pyrimidin-4-one；7-methyl-pyrido[1,2-a]pyrimidin-4-one
• CAS: 23443-20-1
• 化学式: C₉H₈N₂O
• 分子量: 160.175
• InChiKey: DXUYOKHGAJQVQS-UHFFFAOYSA-N

物化性质

• 保留指数：
  1696

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  7-甲基-4H-吡啶并[1,2-A]嘧啶-4-酮 在 tetrabutylammonium tetrafluoroborate 、 sodium chloride 作用下， 以 水 、 丙酮 为溶剂， 以94 %的产率得到3-chloro-7-methyl-4H-pyrido[1,2-a]pyrimidin-4-one
  参考文献：
  名称：

  4H-吡啶并[1,2-a]嘧啶-4-酮的无催化剂和无氧化剂电化学区域选择性卤化和三氟甲基化

  摘要：

  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。

  DOI：

  10.1002/ejoc.202300268
• 作为产物：
  描述：

  ((5-甲基-2-吡啶氨基)亚甲基)丙二酸二乙酯 以 四氢呋喃 、 水 为溶剂， 390.0 ℃ 、12.0 MPa 条件下， 以82%的产率得到7-甲基-4H-吡啶并[1,2-A]嘧啶-4-酮
  参考文献：
  名称：

  在自动化的高温高压流动反应器中合成熔融的嘧啶酮和喹诺酮衍生物

  摘要：

  在自动化的Phoenix高温高压连续流反应器中，数分钟之内即可合成出对药物研究潜在感兴趣的熔融嘧啶酮和喹诺酮衍生物，收率高达96％。难于合成或需要多步操作的杂环支架可使用一组常见的反应条件轻松获得。低沸点溶剂的使用以及这些反应的高转化率使得易于后处理和分离。本文报道的方法高度适合于快速和有效的杂环合成以及化合物的放大。

  DOI：

  10.1021/acs.joc.6b02520

文献信息

• Iodine-Catalyzed Regioselective Sulfenylation of 4H-Pyrido[1,2-a]pyrimidin-4-ones with Sulfonyl Hydrazides
  作者：Shaohua Wang、Wenjie Liu、Zhihao Cai、Ziying Li、Jianwen Liu、Anda Wang

  DOI：10.1055/s-0036-1588549

  日期：2018.1

  A simple and efficient method for direct sulfenylation of 4H-pyrido[1,2-a]pyrimidin-4-ones with sulfonyl hydrazides has been developed. The transformation is catalyzed by iodine under metal-free conditions with high regioselectivity and good functional-group tolerance.

  已经开发了一种简单有效的方法，用于 4H-吡啶并 [1,2-a] 嘧啶-4-酮与磺酰肼的直接磺基化。该转化在无金属条件下由碘催化，具有高区域选择性和良好的官能团耐受性。
• Enantioselective hydrogenation of annulated arenes: controlled formation of multiple stereocenters in adjacent rings
  作者：Mario P. Wiesenfeldt、Daniel Moock、Daniel Paul、Frank Glorius

  DOI：10.1039/d0sc07099h

  日期：——

  hydrogenation of annulated arenes using 4H-pyrido[1,2-a]pyrimidinones as substrates. The method selectively generates multiple stereocenters in adjacent rings leading to architecturally complex motifs, which resemble bioactive molecules. The mechanistic study of the stereochemical outcome revealed that the catalyst is able to overcome substrate stereocontrol providing all-cis-substituted products predominantly

  我们报告了一种使用 4 H-吡啶并[1,2- a ]嘧啶酮作为底物对环状芳烃进行对映选择性氢化的方法。该方法选择性地在相邻环中生成多个立体中心，从而形成结构复杂的图案，类似于生物活性分子。立体化学结果的机理研究表明，该催化剂能够克服底物立体控制，主要提供全顺式取代的产物。在顺序方案中，实现了催化剂和底物立体控制之间的匹配相互作用，这有利于非对映和对映选择性获得反式产物。
• Regioselective C3 Alkenylation of 4 <i>H</i>-pyrido[1,2-<i>a</i>]pyrimidin-4-ones via Palladium-Catalyzed CH Activation
  作者：Wenjie Liu、Shaohua Wang、Qi Zhang、Jingwen Yu、Jiahe Li、Zhiwei Xie、Hua Cao

  DOI：10.1002/asia.201402455

  日期：2014.9

  A general and efficient palladium‐catalyzed direct C3 alkenylation of 4H‐pyrido[1,2‐a]pyrimidin‐4‐ones using AgOAc/O2 as the oxidant has been developed. A variety of 4H‐pyrido[1,2‐a]pyrimidin‐4‐ones were successfully coupled with acrylate esters, styrenes, methylvinylketone, and acrylamide in moderate to excellent yields. The reaction exhibited complete regio‐ and stereoselectivity. This transformation

  已经开发了一种以AgOAc / O 2为氧化剂的4 H-吡啶并[1,2 - a ]嘧啶-4-酮的普通钯催化的直接C3烯基化反应。各种4 H-吡啶并[1,2 - a ]嘧啶-4-酮已成功与丙烯酸酯，苯乙烯，甲基乙烯基酮和丙烯酰胺偶联，产率中等至优异。该反应显示出完全的区域选择性和立体选择性。该转化提供了一种有吸引力的新方法，可对4个H-吡啶并[1,2- a ]嘧啶-4-酮进行功能化。
• Pd-Catalyzed Ag(I)-Promoted C3-Arylation of Pyrido[1,2-<i>a</i>]pyrimidin-4-ones with Bromo/Iodo-Arenes
  作者：Sankar K. Guchhait、Garima Priyadarshani

  DOI：10.1021/acs.joc.5b01573

  日期：2015.8.21

  A regioselective Ag(I)-promoted Pd-catalyzed C3-H activation arylation of pyrido[1,2-a]pyrimidin-4-ones with bromo/iodo-(hetero)arenes under aqueous conditions has been developed. It affords an efficient access to pharmaceutically important versatile 3-arylpyrido[1,2-a]pyrimidin-4-ones. Interestingly, the arylation undergoes via a pathway with an unusual feature involving the formation of cationic arylpalladium species promoted by halo-sequestering Ag salts enabling concerted C3-palladation-deprotonation, as explored by relevant experiments and spectroscopic studies. The present approach is step economical, good yielding, and compatible with various functionalities and applicable to a wide range of starting materials.
• 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.