diethyl <4-(dimethylamino)phenyl>propanedioate | 83026-39-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: diethyl <4-(dimethylamino)phenyl>propanedioate
• 英文别名: 2-(4-dimethylaminophenyl)malonic acid diethyl ester；diethyl 2-(4-dimethylaminophenyl)malonate；Diethyl 2-[4-(dimethylamino)phenyl]propanedioate
• CAS: 83026-39-5
• 化学式: C₁₅H₂₁NO₄
• 分子量: 279.336
• InChiKey: WKHJVWBFFOYEKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diethyl <4-(dimethylamino)phenyl>propanedioate 在 sodium ethanolate 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 生成 [4-(4,6-dichloropyrimidin-5-yl)phenyl]dimethylamine
  参考文献：
  名称：

  4-Amino-5-aryl-6-arylethynylpyrimidines: Structure–activity relationships of non-nucleoside adenosine kinase inhibitors

  摘要：

  A series of non-nucleoside adenosine kinase (AK) inhibitors is reported. These inhibitors originated from the modification of 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine (ABT-702). The identification of a linker that would approximate the spatial arrangement found between the pyrimidine ring and the aryl group at C(7) in ABT702 was a key element in this modification. A search of potential linkers led to the discovery of an acetylene moiety as a suitable scaffold. It was hypothesized that the aryl acetylenes, ABT-702, and adenosine bound to the active site of AK (closed form) in a similar manner with respect to the orientation of the heterocyclic base. Although potent acetylene analogs were discovered based on this assumption, an X-ray crystal structure of 5-(4-dimethylaminophenyl)-6-(6-morpholin-4-yipyridin-3-ylethynyl)pyrimidin-4-ylamine (16a) revealed a binding orientation contrary to adenosine. In addition, this compound bound tightly to a unique open conformation of AK. The structure-activity relationships and unique ligand orientation and protein conformation are discussed. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.12.029
• 作为产物：
  描述：

  4-(二甲氨基)苯乙酸 在 氯化亚砜 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 4.0h， 生成 diethyl <4-(dimethylamino)phenyl>propanedioate
  参考文献：
  名称：

  4-Amino-5-aryl-6-arylethynylpyrimidines: Structure–activity relationships of non-nucleoside adenosine kinase inhibitors

  摘要：

  A series of non-nucleoside adenosine kinase (AK) inhibitors is reported. These inhibitors originated from the modification of 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine (ABT-702). The identification of a linker that would approximate the spatial arrangement found between the pyrimidine ring and the aryl group at C(7) in ABT702 was a key element in this modification. A search of potential linkers led to the discovery of an acetylene moiety as a suitable scaffold. It was hypothesized that the aryl acetylenes, ABT-702, and adenosine bound to the active site of AK (closed form) in a similar manner with respect to the orientation of the heterocyclic base. Although potent acetylene analogs were discovered based on this assumption, an X-ray crystal structure of 5-(4-dimethylaminophenyl)-6-(6-morpholin-4-yipyridin-3-ylethynyl)pyrimidin-4-ylamine (16a) revealed a binding orientation contrary to adenosine. In addition, this compound bound tightly to a unique open conformation of AK. The structure-activity relationships and unique ligand orientation and protein conformation are discussed. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.12.029

文献信息

• Arylation of diethyl malonate and ethyl cyanoacetate catalyzed by palladium/di-tert-butylneopentylphosphine
  作者：Jeffrey G. Semmes、Stephanie L. Bevans、C. Haddon Mullins、Kevin H. Shaughnessy

  DOI：10.1016/j.tetlet.2015.01.072

  日期：2015.6

  α-Arylated carbonyl derivatives are important structural motifs in many natural products and pharmaceutically active compounds. Although arylation of simple monocarbonyl compounds is a well-established methodology, metal-catalyzed arylation of β-dicarbonyl derivatives is significantly more challenging. The ability of β-dicarbonyl anions to bind to palladium in a κ2-O,O mode, rather than the κ1-C-bound

  在许多天然产物和药物活性化合物中，α-芳基化羰基衍生物是重要的结构基序。尽管简单的单羰基化合物的芳基化是一种公认​​的方法，但金属催化的β-二羰基衍生物的芳基化更具挑战性。β二羰基的阴离子结合至钯在κ的能力2 - ø，ö模式，而不是κ 1 - c ^结合的模式键形成所需的，经常导致催化剂体系的失活。烯醇盐的C-结合形式可通过使用空间需求的配体来促进。在此，我们报告中指出，空间要求的二叔丁基丁基新戊基膦（DTBNpP）配体与Pd（dba）2结合为芳基溴化物和氯化物与丙二酸二乙酯的偶联提供了有效的催化剂。Pd / DTBNpP系统还催化芳基溴化物与氰基乙酸乙酯的偶联。
• Palladium-Catalyzed Arylation of Malonates and Cyanoesters Using Sterically Hindered Trialkyl- and Ferrocenyldialkylphosphine Ligands
  作者：Neil A. Beare、John F. Hartwig

  DOI：10.1021/jo016226h

  日期：2002.1.1

  diethyl malonate, di-tert-butyl malonate, diethyl fluoromalonate, ethyl cyanoacetate, and ethyl phenylcyanoacetate. Although alkyl malonates and ethyl alkylcyanoacetates did not react with aryl halides using these catalysts, the same products were formed conveniently in one pot from diethylmalonate by cross-coupling of an aryl halide in the presence of excess base and subsequent alkylation.

  据报道，钯催化的芳基溴化物和氯化物与两种常见的稳定化碳负离子（丙二酸二烷基酯和烷基氰基酸酯的烯醇盐）的反应。对这些反应的范围进行了探索，并且表明该过程以一般方式发生。使用P（t-Bu）（3）（1），五苯基二茂铁基配体（Ph（5）C（5））Fe（C（5）H（4））P（t-Bu）（2）（2） ，或金刚烷基配体（1-Ad）P（t-Bu）（2）（3），表明贫电子和富电子，空间受阻且不受阻碍的芳基溴化物和氯化物与丙二酸二乙酯丙二酸叔丁酯，氟丙二酸二乙酯，氰基乙酸乙酯和苯基氰基乙酸乙酯。尽管使用这些催化剂的丙二酸烷基酯和烷基氰基乙酸乙酯不与芳基卤化物反应，
• Ester enolates from .alpha.-acetoxy esters. Synthesis of arylmalonic and .alpha.-arylalkanoic esters from aryl nucleophiles and .alpha.-keto esters
  作者：Subrata Ghosh、Simon N. Pardo、Robert G. Salomon

  DOI：10.1021/jo00145a017

  日期：1982.11
• GHOSH, S.;PARDO, S. N.;SALOMON, R. G., J. ORG. CHEM., 1982, 47, N 24, 4692-4702
  作者：GHOSH, S.、PARDO, S. N.、SALOMON, R. G.

  DOI：——

  日期：——
• 4-Amino-5-aryl-6-arylethynylpyrimidines: Structure–activity relationships of non-nucleoside adenosine kinase inhibitors
  作者：Mark A. Matulenko、Ernest S. Paight、Robin R. Frey、Arthur Gomtsyan、Stanley DiDomenico、Meiqun Jiang、Chih-Hung Lee、Andrew O. Stewart、Haixia Yu、Kathy L. Kohlhaas、Karen M. Alexander、Steve McGaraughty、Joseph Mikusa、Kennan C. Marsh、Steven W. Muchmore、Clarissa L. Jakob、Elizabeth A. Kowaluk、Michael F. Jarvis、Shripad S. Bhagwat

  DOI：10.1016/j.bmc.2006.12.029

  日期：2007.2

  A series of non-nucleoside adenosine kinase (AK) inhibitors is reported. These inhibitors originated from the modification of 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine (ABT-702). The identification of a linker that would approximate the spatial arrangement found between the pyrimidine ring and the aryl group at C(7) in ABT702 was a key element in this modification. A search of potential linkers led to the discovery of an acetylene moiety as a suitable scaffold. It was hypothesized that the aryl acetylenes, ABT-702, and adenosine bound to the active site of AK (closed form) in a similar manner with respect to the orientation of the heterocyclic base. Although potent acetylene analogs were discovered based on this assumption, an X-ray crystal structure of 5-(4-dimethylaminophenyl)-6-(6-morpholin-4-yipyridin-3-ylethynyl)pyrimidin-4-ylamine (16a) revealed a binding orientation contrary to adenosine. In addition, this compound bound tightly to a unique open conformation of AK. The structure-activity relationships and unique ligand orientation and protein conformation are discussed. (c) 2006 Elsevier Ltd. All rights reserved.