3-cyano-2,6-dimethoxy-5-ethyl-4-methylpyridine | 252950-80-4

• 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: 3-cyano-2,6-dimethoxy-5-ethyl-4-methylpyridine
• 英文别名: 5-Ethyl-2,6-dimethoxy-4-methylpyridine-3-carbonitrile
• CAS: 252950-80-4
• 化学式: C₁₁H₁₄N₂O₂
• 分子量: 206.244
• InChiKey: DRZHPMMUJLCRIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  55.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-cyano-2,6-dimethoxy-5-ethyl-4-methylpyridine 在 吡啶 、 lithium diisopropyl amide 、 三氯氧磷 作用下， 以 四氢呋喃 为溶剂， 反应 1.17h， 生成 4-(3,5-Dimethylbenzyl)-5-ethyl-2,6-dimethoxynicotinonitrile
  参考文献：
  名称：

  Syntheses of 4-Benzylpyridones via Nucleophilic Aromatic Substitutions

  摘要：

  研究了制备有效联芳基甲烷非核苷逆转录酶抑制剂类似物的不同策略。我们研究了3-氰基-4-(3,5-二甲基苄基)-5-乙基-6-羟基吡啶-2(1H)-酮及其环状类似物4-(3,5)的可能制备路线。 -二甲基苄基)-6-氧代-2,3,6,7-四氢呋喃[2,3-b]吡啶-5-甲腈。前者的制备是由 4-甲基-5-乙基-2,6-二甲氧基烟腈的阴离子通过 3,5-二甲基碘苯上的亲核芳香取代反应或从 3,5-二甲基环己酮上的亲核加成反应开始实现的。环状类似物是通过前所未有的亲核芳族取代制备的，例如 3,5-二甲基碘苯与 4-甲基-6-氧代-2,3,6,7-四氢呋喃[2,3-b]吡啶-二价阴离子5-甲腈。本文描述的新化合物均未在细胞测定（CEM-SS和MT4）中显示出抗HIV-1活性或细胞毒性。

  DOI：

  10.1055/s-2001-17526
• 作为产物：
  描述：

  碘甲烷 、 原甲酸三甲酯 、 5-ethyl-2,6-dihydroxy-4-methyl-nicotinonitrile 在 Montmorillonite K₁₀ 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以82%的产率得到3-cyano-2,6-dimethoxy-5-ethyl-4-methylpyridine
  参考文献：
  名称：

  On the methylation of 3-cyano-6-hydroxypyridine-2(1H)-ones

  摘要：

  In order to prepare new heterocyclic derivatives as building block for compounds with potential biological activities, we were led to study the O-methylation of 3-cyano-6-hydroxypyridine-2(1H)-ones such as 1. This enabled us to develop a new two steps method to prepare the corresponding 2,6-dimethoxy derivative 5 in 80 % yield. It consisted first in heating 1 in trimethylorthoformate, with or without an acidic catalyst, which gave a mixture of the two mono-methoxy isomers, then a classical methylation of the second hydroxy moiety led almost exclusively to 5. In this paper we present this "methylation" method and various unexpected results recorded when we attempted to extend it to related derivatives or to other heterocycle containing lactim-lactam functions. An intramolecular transetherification mechanism requiring the simultaneous transfer of a hydrogen and a methyl is suggested. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(99)00755-3

文献信息

• On the methylation of 3-cyano-6-hydroxypyridine-2(1H)-ones
  作者：Yves Louis Janin、Jaouad Chiki、Michel Legraverend、Christiane Huel、Emile Bisagni

  DOI：10.1016/s0040-4020(99)00755-3

  日期：1999.10

  In order to prepare new heterocyclic derivatives as building block for compounds with potential biological activities, we were led to study the O-methylation of 3-cyano-6-hydroxypyridine-2(1H)-ones such as 1. This enabled us to develop a new two steps method to prepare the corresponding 2,6-dimethoxy derivative 5 in 80 % yield. It consisted first in heating 1 in trimethylorthoformate, with or without an acidic catalyst, which gave a mixture of the two mono-methoxy isomers, then a classical methylation of the second hydroxy moiety led almost exclusively to 5. In this paper we present this "methylation" method and various unexpected results recorded when we attempted to extend it to related derivatives or to other heterocycle containing lactim-lactam functions. An intramolecular transetherification mechanism requiring the simultaneous transfer of a hydrogen and a methyl is suggested. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Syntheses of 4-Benzylpyridones via Nucleophilic Aromatic Substitutions
  作者：Yves L. Janin、Christiane Huel、Michel Legraverend、Anne-Marie Aubertin、Emile Bisagni

  DOI：10.1055/s-2001-17526

  日期：——

  Different strategies were studied for the preparation of analogues of potent biarylmethanes non-nucleoside reverse transcriptase inhibitors. We undertook the study of the possible routes for the preparation of 3-cyano-4-(3,5-dimethylbenzyl)-5-ethyl-6-hydroxypyridin-2(1H)-one and its cyclic analogue 4-(3,5-dimethylbenzyl)- 6-oxo- 2,3,6,7 - tetrahydrofuro [2,3 - b] pyridine-5 - carboni-trile. Preparation of the former was achieved from the anion of 4-methyl-5-ethyl-2,6-dimethoxynicotinonitrile either by a nucleophilic aromatic substitution reaction on 3,5-dimethyl iodobenzene or starting with a nucleophilic addition reaction on 3,5-dimethylcyclohexanone. Cyclic analogues were prepared by an unprecedented nucleophilic aromatic substitution of, for example, 3,5-dimethyliodobenzene with the dianion of 4-methyl-6-oxo-2,3,6,7-tetrahydrofuro[2,3-b]pyridine-5-carbonitrile. None of the herein described new compounds showed anti HIV-1 activity or cytotoxicity on cellular assays (CEM-SS and MT4).

  研究了制备有效联芳基甲烷非核苷逆转录酶抑制剂类似物的不同策略。我们研究了3-氰基-4-(3,5-二甲基苄基)-5-乙基-6-羟基吡啶-2(1H)-酮及其环状类似物4-(3,5)的可能制备路线。 -二甲基苄基)-6-氧代-2,3,6,7-四氢呋喃[2,3-b]吡啶-5-甲腈。前者的制备是由 4-甲基-5-乙基-2,6-二甲氧基烟腈的阴离子通过 3,5-二甲基碘苯上的亲核芳香取代反应或从 3,5-二甲基环己酮上的亲核加成反应开始实现的。环状类似物是通过前所未有的亲核芳族取代制备的，例如 3,5-二甲基碘苯与 4-甲基-6-氧代-2,3,6,7-四氢呋喃[2,3-b]吡啶-二价阴离子5-甲腈。本文描述的新化合物均未在细胞测定（CEM-SS和MT4）中显示出抗HIV-1活性或细胞毒性。

表征谱图