N-isopropenyloxyphthalimide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: N-isopropenyloxyphthalimide
• 英文别名: 2-Prop-1-en-2-yloxyisoindole-1,3-dione；2-prop-1-en-2-yloxyisoindole-1,3-dione
• 化学式: C₁₁H₉NO₃
• 分子量: 203.197
• InChiKey: RPEFHWBWYJDQAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-isopropenyloxyphthalimide 在 甲基肼 作用下， 以 二氯甲烷 为溶剂， 生成 C₃H₇NO
  参考文献：
  名称：

  The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901

  摘要：

  A novel series of benzhydroxamate esters derived from their precursor anthranilic acids have been prepared and have been identified as potent MEK inhibitors. 2-(2-Chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3,4-difluoro-benzamide, CI-1040, was the first MEK inhibitor to demonstrate in vivo activity in preclinical animal models and subsequently became the first MEK inhibitor to enter clinical trial. CI-1040 suffered however from poor exposure due to its poor solubility and rapid clearance, and as a result, development of the compound was terminated. Optimization of the diphenylamine core and modi. cation of the hydroxamate side chain for cell potency, solubility, and exposure with oral delivery resulted in the discovery of the clinical candidate N-(2,3-dihydroxy-propoxy)-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzamide PD 0325901. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.054
• 作为产物：
  描述：

  N-羟基邻苯二甲酰亚胺 、 丙-1-烯-2-醇 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 生成 N-isopropenyloxyphthalimide
  参考文献：
  名称：

  The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901

  摘要：

  A novel series of benzhydroxamate esters derived from their precursor anthranilic acids have been prepared and have been identified as potent MEK inhibitors. 2-(2-Chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3,4-difluoro-benzamide, CI-1040, was the first MEK inhibitor to demonstrate in vivo activity in preclinical animal models and subsequently became the first MEK inhibitor to enter clinical trial. CI-1040 suffered however from poor exposure due to its poor solubility and rapid clearance, and as a result, development of the compound was terminated. Optimization of the diphenylamine core and modi. cation of the hydroxamate side chain for cell potency, solubility, and exposure with oral delivery resulted in the discovery of the clinical candidate N-(2,3-dihydroxy-propoxy)-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzamide PD 0325901. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.054

文献信息

• Regio‐ and Stereoselective Chan‐Lam‐Evans Enol Esterification of Carboxylic Acids with Alkenylboroxines
  作者：Luuk Steemers、Linda Wijsman、Jan H. van Maarseveen

  DOI：10.1002/adsc.201800914

  日期：2018.11.5

  Efficient and scalable Cu(II)‐mediated enol esterification methodology of carboxylic acids from alkenyl boroxines and boronic acids is presented. The reaction shows a wide scope in aliphatic and aromatic carboxylic acids in combination with several alkenyl boroxines. In the case of 2‐substituted alkenyl boroxines the double bond configuration was fully retained in the enol ester product. Also N‐hydroxyimides

  提出了一种高效，可扩展的Cu（II）介导的烯基环硼氧烷和硼酸羧酸的烯醇酯化方法。该反应在脂肪族和芳香族羧酸与几种烯基环硼氧烷化合物的组合中显示出广泛的范围。对于2取代的烯基硼氧烷，双键构型完全保留在烯醇酯产品中。N-羟基酰亚胺和酰亚胺也可以在相应的酰氧基乙烯基烯醇醚和乙烯基酰胺中转化。最后，除甲硫氨酸外，所有其他19种规范氨基酸都显示出它们的相容性，从而以立体选择性方式生成烯醇酯。
• <i>O</i>-Cyclopropyl hydroxylamines: gram-scale synthesis and utility as precursors for N-heterocycles
  作者：Kaitlyn Lovato、Urmibhusan Bhakta、Yi Pin Ng、László Kürti

  DOI：10.1039/d0ob00611d

  日期：——

  O-Cyclopropyl hydroxylamines, now accessible via a novel and scalable synthetic route, have been demonstrated to be bench-stable and practical precursors for the synthesis of N-heterocycles via a di-heteroatom [3,3]-sigmatropic rearrangement. In order to study the reactivity of these compounds in depth, a robust synthesis of both ring-substituted and ring-unsubstituted O-cyclopropyl hydroxylamines has

  O-环丙基羟胺，现在可以通过新颖且可扩展的合成途径获得，已证明是通过二杂原子[3,3]-σ重排合成N-杂环的替补稳定且实用的前体。为了深入研究这些化合物的反应性，已经开发了环取代和环未取代的O-环丙基羟胺的稳健合成。还确定了这些前体易于N-芳基化的无金属条件。发现N-芳基化的O-环丙基异羟肟酸酯可以在碱介导的条件下有效地经历一锅[3,3]-σ重排/环化/芳构化级联反应，以提供一组结构多样的取代四氢喹啉。
• US8741291B2
  申请人：——

  公开号：US8741291B2

  公开（公告）日：2014-06-03
• The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901
  作者：Stephen D. Barrett、Alexander J. Bridges、David T. Dudley、Alan R. Saltiel、James H. Fergus、Cathlin M. Flamme、Amy M. Delaney、Michael Kaufman、Sophie LePage、Wilbur R. Leopold、Sally A. Przybranowski、Judith Sebolt-Leopold、Keri Van Becelaere、Annette M. Doherty、Robert M. Kennedy、Dan Marston、W. Allen Howard、Yvonne Smith、Joseph S. Warmus、Haile Tecle

  DOI：10.1016/j.bmcl.2008.10.054

  日期：2008.12

  A novel series of benzhydroxamate esters derived from their precursor anthranilic acids have been prepared and have been identified as potent MEK inhibitors. 2-(2-Chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3,4-difluoro-benzamide, CI-1040, was the first MEK inhibitor to demonstrate in vivo activity in preclinical animal models and subsequently became the first MEK inhibitor to enter clinical trial. CI-1040 suffered however from poor exposure due to its poor solubility and rapid clearance, and as a result, development of the compound was terminated. Optimization of the diphenylamine core and modi. cation of the hydroxamate side chain for cell potency, solubility, and exposure with oral delivery resulted in the discovery of the clinical candidate N-(2,3-dihydroxy-propoxy)-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzamide PD 0325901. (C) 2008 Elsevier Ltd. All rights reserved.