N1-(4-吡啶基)苯甲酰胺 | 5221-44-3

• 物质功能分类: 医药中间体 - 杂环化合物 - 吡啶类化合物
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N1-(4-吡啶基)苯甲酰胺
• 英文名称: N-(pyridin-4-yl)benzamide
• 英文别名: 4-benzamidopyridine；N-(4-pyridyl)benzamide；4-Benzoylamino-pyridin；N-(4-pyridinyl)benzamide；4-benzoylaminopyridine；N-(pyrid-4-yl)benzamide；4-Benzamido-pyridin；N-pyridin-4-ylbenzamide
• CAS: 5221-44-3
• 化学式: C₁₂H₁₀N₂O
• mdl: MFCD00160355
• 分子量: 198.224
• InChiKey: PNWVOLKZHJEWQU-UHFFFAOYSA-N

物化性质

• 熔点：
  210 °C

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  N1-(4-吡啶基)苯甲酰胺 在 五氧化二氮 作用下， 以 硝基甲烷 为溶剂， 反应 0.5h， 以63%的产率得到N-(3-硝基吡啶-4-基)苯甲酰胺
  参考文献：
  名称：

  通过4-酰基氨基吡啶的硝化合成3,4-二氨基吡啶和咪唑并[4,5- c ]吡啶

  摘要：

  探索了基于4-酰基氨基吡啶3a，3b直接硝化制备3,4-二氨基吡啶（5）和咪唑并[4,5- c ]吡啶7a，7b的新方法。

  DOI：

  10.1002/jhet.5570360505
• 作为产物：
  描述：

  苯甲酸 在 草酰氯 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 N1-(4-吡啶基)苯甲酰胺
  参考文献：
  名称：

  Discovery of methoxy-naphthyl linked N-(1-benzylpiperidine) benzamide as a blood-brain permeable dual inhibitor of acetylcholinesterase and butyrylcholinesterase

  摘要：

  The cholinesterase enzymes play a vital role in maintaining balanced levels of the neurotransmitter acetylcholine in the central nervous system. However, the overexpression of these enzymes results in hampered neurotransmission. Both the major forms of cholinesterase enzymes viz. acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) play a crucial role in blocking neurotransmission; therefore, in recent years, a strategy of dual cholinesterase inhibition is being explored. Herein, we developed an energy-optimized e-pharmacophore hypothesis AHHPRR from AChE-donepezil complex and screened a set of 15 scaffolds that were designed imaginarily. The ligand with N-(1-benzylpyridinium) benzamide framework has shown the highest fitness and volume score, which was chosen for synthesis and validation. A series of pyridinium benzamides were synthesized and screened for cholinesterase inhibition that led to the identification of 7b, a naphthalene containing N-(1-benzylpiperidine) benzamide as a potent dual AChE and BChE inhibitor with IC₅₀ values of 0.176, and 0.47 μM, respectively. The kinetic study indicated that 7b inhibits AChE in a non-competitive manner with Ki value of 0.21 μM, and BChE in a mixed-fashion with Ki of 0.15 μM. The observed mode of inhibition was corroborated with molecular docking studies. The MD simulation studies pointed out that both AChE and BChE undergo low conformational changes in complex with 7b. The benzamide 7b displayed high BBB permeability in PAMPA assay, which indicates its potential for further exploration in preclinical studies for Alzheimer's disease.

  DOI：

  10.1016/j.ejmech.2020.112761

文献信息

• <i>N</i>-Ammonium Ylide Mediators for Electrochemical C–H Oxidation
  作者：Masato Saito、Yu Kawamata、Michael Meanwell、Rafael Navratil、Debora Chiodi、Ethan Carlson、Pengfei Hu、Longrui Chen、Sagar Udyavara、Cian Kingston、Mayank Tanwar、Sameer Tyagi、Bruce P. McKillican、Moses G. Gichinga、Michael A. Schmidt、Martin D. Eastgate、Massimiliano Lamberto、Chi He、Tianhua Tang、Christian A. Malapit、Matthew S. Sigman、Shelley D. Minteer、Matthew Neurock、Phil S. Baran

  DOI：10.1021/jacs.1c03780

  日期：2021.5.26

  taking a first-principles approach guided by computation, these new mediators were identified and rapidly expanded into a library using ubiquitous building blocks and trivial synthesis techniques. The ylide-based approach to C–H oxidation exhibits tunable selectivity that is often exclusive to this class of oxidants and can be applied to real-world problems in the agricultural and pharmaceutical sectors

  强 C(sp 3 )-H 键的位点特异性氧化在有机合成中具有无可争议的效用。从简化对代谢物的获取和先导化合物的后期多样化到截断逆合成计划，学术界和工业界都越来越需要新的试剂和方法来实现这种转变。当前化学试剂的一个主要缺点是在结构和反应性方面缺乏多样性，这阻碍了用于快速筛选的组合方法的使用。在这方面，定向进化仍然最有希望在各种复杂环境中实现复杂的 C-H 氧化。在此，我们提出了一个设计合理的平台，该平台使用N-铵叶立德作为电化学驱动的氧化剂，用于位点特异性、化学选择性 C(sp 3 )-H 氧化。通过采用以计算为指导的第一性原理方法，这些新的介质被识别出来，并使用无处不在的构建块和简单的合成技术迅速扩展到一个库中。基于叶立德的 C-H 氧化方法表现出可调的选择性，这通常是此类氧化剂独有的，可应用于农业和制药领域的实际问题。
• A Cross-Coupling Approach to Amide Bond Formation from Esters
  作者：Taoufik Ben Halima、Jaya Kishore Vandavasi、Mohanad Shkoor、Stephen G. Newman

  DOI：10.1021/acscatal.7b00245

  日期：2017.3.3

  A palladium-catalyzed cross-coupling between aryl esters and anilines is reported, enabling access to diverse amides. The reaction takes place via activation of the C–O bond by oxidative addition with a Pd–NHC complex, which enables the use of relatively non-nucleophilic anilines that otherwise require stoichiometric activation with strong bases in order to react. High yields of aromatic, aliphatic

  据报道，钯催化的芳基酯和苯胺之间的交叉偶联，使得能够获得各种酰胺。反应是通过Pd-NHC络合物的氧化加成激活C-O键来进行的，这使得能够使用相对非亲核的苯胺，否则需要化学计量的活化才能使强碱发生反应。获得高产率的芳族，脂族和杂环产物。在存在和不存在催化剂的情况下评估了一系列活化酯，这表明催化方法大大增加了在不存在苛刻碱的情况下可用于酰胺键形成的亲电试剂的类型。
• Efficient and Mild Ullmann-Type N-Arylation of Amides, Carbamates, and Azoles in Water
  作者：Maud Bollenbach、Pedro G. V. Aquino、João Xavier de Araújo-Júnior、Jean-Jacques Bourguignon、Frédéric Bihel、Christophe Salomé、Patrick Wagner、Martine Schmitt

  DOI：10.1002/chem.201700832

  日期：2017.10.4

  A simple, sustainable, efficient, mild, and low‐cost protocol was developed for d‐glucose‐assisted Cu‐catalyzed Ullmann reactions in water for amides, carbamates, and nitrogen‐containing heterocycles. The reaction was compatible with diverse aryl/heteroaryl iodides, giving highly substituted pyridine, indole, or indazole rings. This method offers an attractive alternative to existing protocols, because

  开发了一种简单，可持续，高效，温和且低成本的方案，用于葡萄糖在水中的酰胺，氨基甲酸酯和含氮杂环的d葡萄糖辅助的Ullmann反应。该反应与各种芳基/杂芳基碘化物相容，得到高度取代的吡啶，吲哚或吲唑环。该方法为现有方案提供了一种有吸引力的替代方法，因为该反应在水性介质中进行，在环境温度或接近环境温度的条件下进行，并提供高收率或高收率的N-芳基化产物。
• Synthesis, Characterization, and Catalytic Activity of Heteroleptic Rhodium Complex for C–N Couplings
  作者：M. N. Zafar、Fouzia Perveen、A. Naz、Ehsan Ullah Mughal、Gul-e-Saba、K. Hina

  DOI：10.1134/s1070328419010135

  日期：2019.1

  AbstractWe have reported synthesis of complex [Rh(COD)(LMe})Cl] (III), where LMe} (II) is N-(1-methylpyridin-4(1H)-ylidene)benzamide and COD is 1,5-cyclooctadiene. Monodentate ligand LMe} was synthesized by deprotonation of [HLMe}][OTf] (I) with sodium hydride. [HLMe}][OTf] was synthesised by methylation of N-(pyridin-4-yl)benzamide (HL) with methyl triflate. All the three synthesized compounds

  摘要我们已经报道了复杂的[Rh（COD）（L Me}）Cl]（III）的合成，其中L Me}（II）是N-（1-甲基吡啶-4（1 H）-亚烷基）苯甲酰胺和COD是1,5-环辛二烯 通过用氢化钠使[HL Me}] [OTf]（I）脱质子合成了单齿配体L Me} 。[HL Me}] [OTf]是通过将N-（吡啶-4-基）苯甲酰胺（HL）与三氟甲磺酸甲酯甲基化而合成的。三种合成的化合物均通过FT-IR，NMR（1 H和13 C），元素分析和MS分析表征。用单晶XRD和计算研究进一步研究了配合物I的结构。复杂我被发现是C–N偶联反应的良好催化剂。分子对接揭示了铑络合物与肌红蛋白的强结合。
• Solvent- and transition metal-free amide synthesis from phenyl esters and aryl amines
  作者：Sergey A. Rzhevskiy、Alexandra A. Ageshina、Gleb A. Chesnokov、Pavel S. Gribanov、Maxim A. Topchiy、Mikhail S. Nechaev、Andrey F. Asachenko

  DOI：10.1039/c8ra10040c

  日期：——

  A general, economical, and environmentally friendly method of amide synthesis from phenyl esters and aryl amines was developed. This new method has significant advantages compared to previously reported palladium-catalyzed approaches. The reaction is performed transition metal- and solvent-free, using a cheap and environmentally benign base, NaH. This approach enabled us to obtain target amides in

  开发了一种由苯酯和芳基胺合成酰胺的通用、经济和环保的方法。与先前报道的钯催化方法相比，这种新方法具有显着优势。该反应在无过渡金属和无溶剂的情况下使用廉价且对环境无害的碱 NaH 进行。这种方法使我们能够以高产率和高原子经济性获得目标酰胺。

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