2-isocyanato-4-methylpyridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-isocyanato-4-methylpyridine
• 英文别名: 2-Isocyanato-4-methylpyridine
• 化学式: C₇H₆N₂O
• 分子量: 134.137
• InChiKey: CTQIOBANNSWTSE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  42.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-苯基-4-甲基-1-戊炔-3醇 、 2-isocyanato-4-methylpyridine 在 三乙胺 作用下， 以 甲苯 为溶剂， 反应 36.0h， 生成 4-methyl-1-phenylpent-1-yn-3-yl (4-methylpyridin-2-yl)carbamate
  参考文献：
  名称：

  咪唑键合的N-杂芳族化合物通过C-N键形成的自由基级联反应的电化学合成

  摘要：

  我们已开发出一种通过杂芳基胺与束缚的内部炔烃的区域特异性电化学（3 + 2）环化反应制备各种咪唑并合的N-杂芳族化合物的统一策略。电合成采用新型的四芳基肼作为催化剂，具有广泛的底物范围，并且不需要过渡金属催化剂和氧化剂。

  DOI：

  10.1002/anie.201711876
• 作为产物：
  描述：

  4-甲基吡啶-2-甲酸 在 氯甲酸乙酯 、 三乙胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 4.0h， 生成 2-isocyanato-4-methylpyridine
  参考文献：
  名称：

  Ouach, Aziz; Boulahjar, Rajâa; Vala, Christine, European Journal of Medicinal Chemistry, 2016, vol. 115, p. 311 - 325

  摘要：

  DOI：

文献信息

• Catalyst-free synthesis of substituted pyridin-2-yl, quinolin-2-yl, and isoquinolin-1-yl carbamates from the corresponding hetaryl ureas and alcohols
  作者：Svetlana O. Kasatkina、Kirill K. Geyl、Sergey V. Baykov、Irina A. Boyarskaya、Vadim P. Boyarskiy

  DOI：10.1039/d1ob00783a

  日期：——

  catalyst-free synthesis of N-pyridin-2-yl, N-quinolin-2-yl, and N-isoquinolin-1-yl carbamates utilizes easily accessible N-hetaryl ureas and alcohols. The proposed environmentally friendly technique is suitable for the good-to-high yielding synthesis of a wide range of N-pyridin-2-yl or N-quinolin-2-yl substituted carbamates featuring electron-donating and electron-withdrawing groups in the azine rings

  N-吡啶-2-基、N-喹啉-2-基和N-异喹啉-1-基氨基甲酸酯的新型无催化剂合成利用容易获得的N-杂芳基脲和醇。所提出的环保技术适用于从良好到高产率合成各种N-吡啶-2-基或N-quinolin-2-yl 取代的氨基甲酸酯，其在吖嗪环中具有给电子和吸电子基团，并且在氧原子处含有各种伯、仲甚至叔烷基取代基（48-94%；31 个例子）。DFT计算和实验研究表明，反应是通过异氰酸异氰酸杂酯中间体的形成进行的。该方法可用于获得N-异喹啉-1-基氨基甲酸酯，但收率较低，苯并[ h ]喹啉-2-基氨基甲酸乙酯也已成功合成（68%）。
• 1H and 13C NMR spectra of some unsymmetric N,N′-dipyridyl ureas: spectral assignments and molecular conformation
  作者：Netai C. Singha、Dixit N. Sathyanarayana

  DOI：10.1039/a606800f

  日期：——

  The 1H NMR spectra of N-(2-pyridyl), N′-(3-pyridyl)ureas and N-(2-pyridyl), N′-(4-pyridyl)ureas in CDCl3 and (CD3)2CO have been assigned with the aid of COSY and NOE experiments and chemical shift and coupling constant correlations. The 13C NMR spectra in CDCl3 were analysed utilizing the HETCOR and proton coupled spectra. The 1H NMR spectra, NOE effects and MINDO/3 calculations have been utilized to show that the molecular conformation of these compounds has the 2-pyridyl ring coplanar with the urea plane with the N–H group hydrogen bonded to the nitrogen of the 2-pyridyl group on the other urea nitrogen while the 3/4-pyridyl group rotates rapidly about the N–C3/N–C4 bond.

  借助 COSY 和 NOE 实验以及化学位移和耦合常数相关性，分配了 N-(2-吡啶基)、Nâ²-(3-吡啶基)脲和 N-(2-吡啶基)、Nâ²-(4-吡啶基)脲在 CDCl3 和 (CD3)2CO 中的 1H NMR 光谱。利用 HETCOR 和质子耦合光谱分析了 CDCl3 中的 13C NMR 光谱。利用 1H NMR 光谱、NOE 效应和 MINDO/3 计算表明，这些化合物的分子构象是 2-吡啶基环与脲平面共面，NâH 基氢键与另一个脲氮上的 2-吡啶基氮相连，而 3/4 吡啶基围绕 NâC3/NâC4 键快速旋转。
• Discovery of novel VEGFR-2 inhibitors. Part 5: Exploration of diverse hinge-binding fragments via core-refining approach
  作者：Yuanyuan Shan、Hongping Gao、Xiaowei Shao、Jinfeng Wang、Xiaoyan Pan、Jie Zhang

  DOI：10.1016/j.ejmech.2015.08.045

  日期：2015.10

  Pathological angiogenesis plays a critical role in numerous diseases including malignancy. VEGFR-2 is the central regulators in angiogenesis and has become a promising target for anticancer drug design. We have identified a novel biphenyl-aryl urea incorporated with salicyladoxime (BPS-7) as potent VEGFR-2 inhibitor. As a continuation to our previous research, various aromatic-heterocyclic were introduced as hinge-binding fragment via a core-refining approach. Interestingly, many compounds exhibited comparable VEGFR-2 inhibition to Sorafenib. In particular, 12e and 12o displayed excellent VEGFR-2 inhibitory activity with IC50 values of 0.50 nM and 0.79 nM, respectively. Several title compounds showed considerable antiproliferative activity against A549 and SMMC-7721 cells. In addition, molecular docking was performed to rationalize the efficiency of the better compounds. These results will be instructive for further inhibitor design and optimization. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Advances in tetrahydropyrido[1,2- a ]isoindolone (valmerins) series: Potent glycogen synthase kinase 3 and cyclin dependent kinase 5 inhibitors
  作者：Rajâa Boulahjar、Aziz Ouach、Stéphane Bourg、Pascal Bonnet、Olivier Lozach、Laurent Meijer、Christiane Guguen-Guillouzo、Rémy Le Guevel、Saïd Lazar、Mohamed Akssira、Yves Troin、Gérald Guillaumet、Sylvain Routier

  DOI：10.1016/j.ejmech.2015.06.046

  日期：2015.8

  An efficient synthetic strategy was developed to modulate the structure of the tetrahydropyridine iso-indolone (Valmerin) skeleton. A library of more than 30 novel final structures was generated. Biological activities on CDK5 and GSM as well as cellular effects on cancer cell lines were measured for each novel compound. Additionally docking studies were performed to support medicinal chemistry efforts. A strong GSK3/CDK5 dual inhibitor (38, IC50 GSK3/CDK5 32/84 nM) was obtained. A set of highly selective GSK3 inhibitors was synthesized by fine-tuning structural modifications (29 IC50 GSK3/CDK5 32/320 nM). Antiproliferative effects on cells were correlated with the in vitro Kinase activities and the best effects were obtained with lung and colon cell lines. (C) 2015 Elsevier Masson SAS. All rights reserved.