7-phenyl-5H-pyrano[4,3-b]pyridin-5-one | 5657-54-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: 7-phenyl-5H-pyrano[4,3-b]pyridin-5-one
• 英文别名: 7-phenyl-5H-pyrano<4,3-b>pyridin-5-one；7-Phenylpyrano[4,3-b]pyridin-5-one
• CAS: 5657-54-5
• 化学式: C₁₄H₉NO₂
• 分子量: 223.231
• InChiKey: YWMJZVFEVBQHBG-UHFFFAOYSA-N

物化性质

• 熔点：
  136-137 °C
• 沸点：
  407.4±45.0 °C(Predicted)
• 密度：
  1.294±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 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：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-phenyl-5H-pyrano[4,3-b]pyridin-5-one 在 氨 作用下， 以 乙二醇甲醚 为溶剂， 以249 mg的产率得到7-phenyl-1,6-naphthyridin-5-one
  参考文献：
  名称：

  Structure-based design, synthesis and evaluation in vitro of arylnaphthyridinones, arylpyridopyrimidinones and their tetrahydro derivatives as inhibitors of the tankyrases

  摘要：

  The tankyrases are members of the PARP superfamily; they poly(ADP-ribosyl) ate their target proteins using NAD(+) as a source of electrophilic ADP-ribosyl units. The three principal protein substrates of the tankyrases (TRF1, NuMA and axin) are involved in replication of cancer cells; thus inhibitors of the tankyrases may have anticancer activity. Using structure-based drug design and by analogy with known 3-arylisoquinolin-1-one and 2-arylquinazolin-4-one inhibitors, series of arylnaphthyridinones, arylpyridinopyrimidinones and their tetrahydro-derivatives were synthesised and evaluated in vitro. 7-Aryl-1,6-naphthyridin-5-ones, 3-aryl-2,6-naphthyridin-1-ones and 3-aryl-2,7-naphthyridin-1-ones were prepared by acid-catalysed cyclisation of the corresponding arylethynylpyridinenitriles or reaction of bromopyridinecarboxylic acids with beta-diketones, followed by treatment with NH3. The 7-aryl-1,6-naphthyridin-5-ones were methylated at 1-N and reduced to 7-aryl-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-ones. Cu-catalysed reaction of benzamidines with bromopyridinecarboxylic acids furnished 2-arylpyrido[2,3-d]pyrimidin-4-ones. Condensation of benzamidines with methyl 1-benzyl-4-oxopiperidine-3-carboxylate and deprotection gave 2-aryl-5,6,7,8-tetrahydropyrido[4,3-d] pyrimidin-4-ones, aza analogues of the known inhibitor XAV939. Introduction of the ring-N in the arylnaphthyridinones and the arylpyridopyrimidinones caused > 1000-fold loss in activity, compared with their carbocyclic isoquinolinone and quinazolinone analogues. However, the 7-aryl-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-ones showed excellent inhibition of the tankyrases, with some examples having IC50 = 2 nM. One compound (7-(4-bromophenyl)-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-one) showed 70-fold selectivity for inhibition of tankyrase-2 versus tankyrase-1. The mode of binding was explored through crystal structures of inhibitors in complex with tankyrase-2. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.005
• 作为产物：
  描述：

  苯乙炔 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 硫酸 、 二异丙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 121.5h， 生成 7-phenyl-5H-pyrano[4,3-b]pyridin-5-one
  参考文献：
  名称：

  Structure-based design, synthesis and evaluation in vitro of arylnaphthyridinones, arylpyridopyrimidinones and their tetrahydro derivatives as inhibitors of the tankyrases

  摘要：

  The tankyrases are members of the PARP superfamily; they poly(ADP-ribosyl) ate their target proteins using NAD(+) as a source of electrophilic ADP-ribosyl units. The three principal protein substrates of the tankyrases (TRF1, NuMA and axin) are involved in replication of cancer cells; thus inhibitors of the tankyrases may have anticancer activity. Using structure-based drug design and by analogy with known 3-arylisoquinolin-1-one and 2-arylquinazolin-4-one inhibitors, series of arylnaphthyridinones, arylpyridinopyrimidinones and their tetrahydro-derivatives were synthesised and evaluated in vitro. 7-Aryl-1,6-naphthyridin-5-ones, 3-aryl-2,6-naphthyridin-1-ones and 3-aryl-2,7-naphthyridin-1-ones were prepared by acid-catalysed cyclisation of the corresponding arylethynylpyridinenitriles or reaction of bromopyridinecarboxylic acids with beta-diketones, followed by treatment with NH3. The 7-aryl-1,6-naphthyridin-5-ones were methylated at 1-N and reduced to 7-aryl-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-ones. Cu-catalysed reaction of benzamidines with bromopyridinecarboxylic acids furnished 2-arylpyrido[2,3-d]pyrimidin-4-ones. Condensation of benzamidines with methyl 1-benzyl-4-oxopiperidine-3-carboxylate and deprotection gave 2-aryl-5,6,7,8-tetrahydropyrido[4,3-d] pyrimidin-4-ones, aza analogues of the known inhibitor XAV939. Introduction of the ring-N in the arylnaphthyridinones and the arylpyridopyrimidinones caused > 1000-fold loss in activity, compared with their carbocyclic isoquinolinone and quinazolinone analogues. However, the 7-aryl-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-ones showed excellent inhibition of the tankyrases, with some examples having IC50 = 2 nM. One compound (7-(4-bromophenyl)-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-one) showed 70-fold selectivity for inhibition of tankyrase-2 versus tankyrase-1. The mode of binding was explored through crystal structures of inhibitors in complex with tankyrase-2. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.005

文献信息

• Modular synthesis of 3-substituted isocoumarins <i>via</i> silver-catalyzed aerobic oxidation/<i>6-endo</i> heterocyclization of <i>ortho</i>-alkynylbenzaldehydes
  作者：Hao Wu、Yi-Chun Wang、Andrey Shatskiy、Qiu-Yan Li、Jian-Quan Liu、Markus D. Kärkäs、Xiang-Shan Wang

  DOI：10.1039/d1ob01065d

  日期：——

  A method involving silver-catalyzed aerobic oxidation/6-endo heterocyclization of ortho-alkynylbenzaldehydes to yield 3-substituted isocoumarins is described. The developed protocol allows convenient access to a range of synthetically useful 3-substituted isocoumarins and related fused heterocyclolactones in good to high yields, using silver tetrafluoroborate as the catalyst, and atmospheric oxygen

  描述了一种涉及银催化的有氧氧化/邻位-炔基苯甲醛的6-endo杂环化以产生 3-取代的异香豆素的方法。所开发的协议允许以良好至高产率方便地获得一系列合成有用的 3-取代异香豆素和相关的稠合杂环内酯，使用四氟硼酸银作为催化剂，大气氧作为终端氧化剂和内环氧的来源。机理研究表明自由基途径的参与。
• Tandem Palladium/Charcoal-Copper(I) Iodide (Pd/C-CuI) Catalyzed Sonogashira Coupling and Intramolecular Cyclization from 2-Bromonicotinic Acid (=2-Bromopyridine-3-carboxylic Acid) and Ethynylarenes to 4-Azaphthalides (=Furo[3,4-b]pyridin-5(7H)-ones) and 5
  作者：Agathe Begouin、Maria-João R. P. Queiroz

  DOI：10.1002/hlca.201100060

  日期：2011.10

  Pd/CPh3PCuI and Et3N in dry dioxane under Ar at 90°, a mixture of 4‐azaphthalides (usually the major product) and 5‐azaisocoumarins was obtained after 3.5 h under normal heating (Schemes 3 and 4; Tables 1 and 2). This mixture of compounds was also obtained with the same catalytic system under microwave (MW) irradiation in only 25 min (Tables 3 and 4). The 1‐ethynyl‐3‐methoxybenzene gave on heating only the corresponding

  制备了几种4-氮杂酞（=呋喃[3,4- b ]吡啶-5（7 H）-one）和5-氮杂异香豆素（= 5 H-吡喃并[4,3 - b ]吡啶-5 -one ） Pd / C介导的Sonogashira串联异质偶联以及2-溴烟酸（= 2-溴吡啶-3-羧酸）与各种乙炔基芳烃或3-乙炔基噻吩的5 exo-dig或6 -endo分子内环化反应。在Pd / C的存在下博士3 P 的CuI和Et 3在90°C的Ar下于干燥的二恶烷中的N，在常规加热下3.5 h后获得4-氮杂酞（通常是主要产物）和5-氮杂异香豆素的混合物（方案3和4；表1和2）。在仅25分钟的微波（MW）辐照下，也用相同的催化系统获得了该化合物的混合物（表3和4）。1-乙炔基-3-甲氧基苯仅加热加热相应的4-氮杂萘化物（表2），而在MW照射下，获得了5 -exo-dig和6 -endo-dig产物（表4））。对于3-乙炔基噻吩，两种方法
• NHC-Catalyzed Oxidative Cyclization Reactions of 2-Alkynylbenzaldehydes under Aerobic Conditions: Synthesis of O-Heterocycles
  作者：Jong Hyub Park、Sachin V. Bhilare、So Won Youn

  DOI：10.1021/ol200481u

  日期：2011.5.6

  An NHC-catalyzed, regio- and stereoselective oxidative cyclization of o-alkynylbenzaldehydes bearing an unactivated alkyne moiety as an internal electrophile has been developed to afford phthalides and isocoumarins. A single organocatalytic system enabled two sequential C−O bond formations to take place in an atom economical manner via highly efficient dual activation. Molecular oxygen in air could

  已开发出具有NHC催化，带有未活化炔烃部分的邻炔基苯甲醛作为内部亲电子试剂的区域和立体选择性氧化环化反应，以提供邻苯二甲酸酯和异香豆素。单一的有机催化系统通过高效的双重活化，以原子经济的方式使两个连续的C-O键形成成为可能。在我们新开发的试剂系统下，空气中的分子氧可以用作氧原子的来源，用于将醛氧化为相应的苯甲酸。
• Transition-metal-free oxidative cyclization reaction of enynals to access pyrane-2-one derivatives
  作者：Farzaneh Ansari、Hormoz Khosravi、Alireza Abbasi Kejani、Mahsa Armaghan、Walter Frank、Saeed Balalaie、Farnaz Jafarpour

  DOI：10.1039/d1ob00726b

  日期：——

  α-pyrone derivatives via the formation of two C–O bonds. In this project, K2S2O8 has been introduced as an efficient oxygen source and C–H functionalization agent in regioselective oxidative cyclization reaction with a relatively broad substrate scope.

  开发了一种新颖且有效的烯醛无金属 C-H 官能化方法，通过形成两个 C-O 键来合成α-吡喃酮衍生物。在该项目中，K 2 S 2 O 8被引入作为区域选择性氧化环化反应中的有效氧源和C-H官能化剂，具有相对广泛的底物范围。
• Application of Organolithium and Related Reagents in Synthesis. Part 11¹. Metallation of 2-Methyl- and 4-Methylnicotinic Acids. A Useful Method for Preparation of AZA-Isocoumarins
  作者：J. Epsztajn、M. W. Płotka、J. Ścianowski

  DOI：10.1080/00397919208019305

  日期：1992.5

  Abstract The metallation (LDA/THF) of 2-methyl- and 4-methylnicotinic acids (1) and (2), and the subsequent reaction of the lithiated species (3) and (4) with carbonyl electrophiles as a synthetic route of 5-aza- and 7-aza-isocoumarins (7), (8), (9) and (10), is described. The isocoumarins (9) and (10) appeared to be readily transformable into the corresponding naphthyridines (11) and (12).

  摘要 2-甲基-和 4-甲基烟酸 (1) 和 (2) 的金属化 (LDA/THF)，以及锂化物质 (3) 和 (4) 与羰基亲电试剂的后续反应，作为 5描述了-氮杂-和7-氮杂-异香豆素(7)、(8)、(9)和(10)。异香豆素 (9) 和 (10) 似乎很容易转化为相应的萘啶 (11) 和 (12)。