2-(isopropylamino)-4H-benzo[d][1,3]oxazin-4-one | 14128-53-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 2-(isopropylamino)-4H-benzo[d][1,3]oxazin-4-one
• 英文别名: 2-isopropylamino-4H-3,1-benzoxazin-4one；2-Isopropylamino-benzo[d][1,3]oxazin-4-one；2-(propan-2-ylamino)-3,1-benzoxazin-4-one
• CAS: 14128-53-1
• 化学式: C₁₁H₁₂N₂O₂
• 分子量: 204.228
• InChiKey: HBHNPPYDPGIZKY-UHFFFAOYSA-N

物化性质

• 熔点：
  150-151 °C
• 沸点：
  321.9±25.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  50.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  Methyl 2-{[(propan-2-yl)carbamoyl]amino}benzoate 在 硫酸 作用下， 反应 3.0h， 生成 2-(isopropylamino)-4H-benzo[d][1,3]oxazin-4-one
  参考文献：
  名称：

  设计和合成4H-3,1-苯并恶嗪-4-酮类化合物作为人类白细胞弹性蛋白酶的有效替代底物抑制剂。

  摘要：

  4H-3,1-Benzoxazin-4-ones是丝氨酸蛋白酶人类白细胞弹性蛋白酶（HL弹性蛋白酶）的替代底物抑制剂，在酶催化过程中形成酰基酶中间体。我们已经使用特定方法合成了多种苯并恶嗪酮，这些特定方法已被调整以实现理论上的考虑而决定的环取代方式。本文参考疏水常数D，碱水解速率kOH-，抑制常数Ki及其组分酰化和脱酰化速率常数kon和koff分别报道了175种苯并恶嗪酮对HL弹性蛋白酶的抑制结果。化合物的范围是可观的。碱水解速率和kon跨度为6，koff覆盖5，ki跨度为8个数量级。在这个大数据集上的多元回归已被用于隔离电子和空间效应以及化合物稳定性和弹性蛋白酶抑制特异的其他因素的作用。本质上，简单的电子参数足以说明碱性水解数据中几乎所有的变化，表明电子因素是此类苯并嗪酮反应性的主要决定因素。显着增强苯并恶嗪酮I效力的因素是R5烷基和R2撤离电子。R 7和R 8中的体积大和化合物疏水性不显着，但是R

  DOI：

  10.1021/jm00164a002

文献信息

• Room-Temperature Palladium-Catalyzed CH Activation:<i>ortho</i>-Carbonylation of Aniline Derivatives
  作者：Chris E. Houlden、Marc Hutchby、Chris D. Bailey、J. Gair Ford、Simon N. G. Tyler、Michel R. Gagné、Guy C. Lloyd-Jones、Kevin I. Booker-Milburn

  DOI：10.1002/anie.200805842

  日期：2009.2.23

  Pd and CO—ureally got me! The title reaction proceeds efficiently at 18 °C under CO (1 atm) with 5 % [Pd(OTs)2(MeCN)2] as precatalyst. Depending on the solvents used, either anthranilates or cyclic imides can be obtained in high yields (see picture, BQ=benzoquinone, Ts=4‐toluenesulfonyl).

  Pd 和 CO - 真的抓住了我！标题反应在 18 °C 下在 CO (1 atm) 下有效进行，使用 5% [Pd(OTs) 2 (MeCN) 2 ] 作为预催化剂。根据所使用的溶剂，可以高产率获得邻氨基苯甲酸酯或环状酰亚胺（见图，BQ=苯醌，Ts=4-甲苯磺酰基）。
• I₂/TBHP-Mediated Oxidative Coupling of Amino-Based Bisnucleophiles and Isocyanides: Access to 2-Aminobenzoxazinones, 2-Aminobenzoxazines, and 2-Aminoquinazolines under Metal-Free Conditions
  作者：Hong-Xia Wang、Tian-Qi Wei、Pei Xu、Shun-Yi Wang、Shun-Jun Ji

  DOI：10.1021/acs.joc.8b02395

  日期：2018.11.2

  An I2/tert-butyl hydroperoxide (TBHP)-mediated oxidative coupling reaction of isocyanides with amino-based bisnucleophiles is described for the synthesis of 2-aminobenzoxazinones, 2-aminobenzoxazines, and 2-aminoquinozolines in moderate to excellent yields. Furthermore, this method provides a simple and practical method to construct potential functionalized biologically active molecules.

  描述了I 2 /叔丁基氢过氧化物（TBHP）介导的异氰酸酯与氨基基双亲核试剂的氧化偶联反应，用于以中等至优异的产率合成2-氨基苯并恶嗪酮，2-氨基苯并恶嗪和2-氨基喹唑啉。此外，该方法提供了一种简单而实用的方法来构建潜在的功能化生物活性分子。
• 4H-3,1-benzoxazin-4-ones and related compounds, pharmaceutical compositions containing them, and processes for their preparation
  申请人：SYNTEX (U.S.A.) INC.

  公开号：EP0147211A2

  公开（公告）日：1985-07-03

  Novel 2-amino-4H-3,1-benzoxazin-4-ones represented by the formula and the pharmaceutically acceptable esters and salts thereof wherein R' is hydrogen or lower alkyl; R2 and R3 are each independently hydrogen, halo, lower alkyl, hydroxy, lower alkoxy, lower thioalkyl, -N02, -N(R')2, -NR'COR', -NHCON(R')2 or -NHCOOR', with the proviso that at least one of R1, R2 and R3 is not hydrogen when X is NHR or NR'COR"; and X is a radical chosen trom in which: R is lower alkyl, lower alkenyl, lower alkynyl, optionally substituted lower cycloalkyl or optionally substituted phenyl lower alkyl; each R' is independently hydrogen or lower alkyl, or lower alkenyl or lower alkynyl where the unsaturated bond is at least one carbon removed from the O or N atom; each R" is independently R, lower alkoxy, NHR' or AOR'; and A is an amino acid residue, or a peptide of 2 to 3 amino acid residues, are useful as enzyme inhibitors in animals.

  式所代表的新型 2-氨基-4H-3,1-苯并恶嗪-4-酮及其药物可接受的酯和盐 其中 R' 为氢或低级烷基 及其药学上可接受的酯和盐，其中 R' 为氢或低级烷基； R2和R3各自独立地为氢、卤代、低级烷基、羟基、低级烷氧基、低级硫代烷基、-N02、-N(R')2、-NR'COR'、-NHCON(R')2或-NHCOOR'、 但当 X 为 NHR 或 NR'COR" 时，R1、R2 和 R3 中至少有一个不是氢；以及 X 是一个基团，选自 其中 R 是低级烷基、低级烯基、低级炔基、任选取代的低级环烷基或任选取代的苯基低级烷基； 每个 R'独立地为氢或低级烷基，或低级烯基或低级炔基，其中不饱和键与 O 原子或 N 原子至少相差一个碳； 每个 R "独立地为 R、低级烷氧基、NHR'或 AOR'；以及 A 是氨基酸残基，或由 2 至 3 个氨基酸残基组成的肽，可用作动物体内的酶抑制剂。
• Palladium-Catalyzed Synthesis of 2-Aminobenzoxazinones by Aerobic Oxidative Coupling of Anthranilic Acids and Isocyanides
  作者：Tjøstil Vlaar、Romano V. A. Orru、Bert U. W. Maes、Eelco Ruijter

  DOI：10.1021/jo401924h

  日期：2013.10.18

  Isocyanides have emerged as valuable C-1 building blocks in palladium catalysis. Their potential has, however, mainly been exploited for the synthesis of amidines and amidine-containing heterocycles. To illustrate the broader applicability of isocyanides, we have recently developed a novel oxidative coupling of diamines and isocyanides furnishing valuable guanidine-containing heterocycles. We here report the extension of this protocol to the coupling of anthranilic acids and isocyanides leading to medicinally relevant 2-aminobenzoxazinones. This is a particularly challenging substrate class for this reaction due to the possibility of undesired decarboxylative pathways and the susceptibility of the products to nucleophilic attack. Therefore, this work underlines the generality and broad potential of the oxidative coupling of bisnucleophiles and isocyanides, facilitating the further implementation of this chemistry in library design.
• Inhibition of HSV-1 protease by benzoxazinones
  作者：Richard L. Jarvest、Martin J. Parratt、Christine M. Debouck、Joselina G. Gorniak、L. John Jennings、Halina T. Serafinowska、James E. Strickler

  DOI：10.1016/0960-894x(96)00455-6

  日期：1996.10

  Benzoxazinones have been discovered which are mechanism based inhibitors of HSV-1 protease with micromolar IC50 values. Formation of a monoadduct consistent with the acyl-enzyme complex was detected by mass spectroscopy. A parallel array synthesis was developed to explore 2-heteroatom substituted SAR. Copyright (C) 1996 Elsevier Science Ltd