N-2,6-dichlorophenyl-acrylamide | 37511-45-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-2,6-dichlorophenyl-acrylamide
• 英文别名: 2,6-dichloroacryanilide；N-<2,6-Dichlor-phenyl>-acrylamid；N-(2,6-Dichlorophenyl)prop-2-enamide
• CAS: 37511-45-8
• 化学式: C₉H₇Cl₂NO
• 分子量: 216.067
• InChiKey: CJLLWSBURLHHJY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-2,6-dichlorophenyl-acrylamide 在 potassium chloride 、 palladium diacetate 四丁基溴化铵 、 sodium acetate 、 sodium carbonate 、 三苯基膦 、 potassium bromide 作用下， 以 水 、 甲苯 为溶剂， 生成 1-(2,6-dichlorophenyl)-5-(2,4-difluorophenyl)-1,6-naphthyridin-2(1H)-one
  参考文献：
  名称：

  Synthesis of a Naphthyridone p38 MAP Kinase Inhibitor

  摘要：

  Compound 1 is a p38 MAP kinase inhibitor potentially useful for the treatment of rheumatoid arthritis and psoriasis. A novel six-step synthesis suitable for large-scale preparation was developed in support of a drug development program at Merck Research Laboratories. The key steps include a tandem Heck-lactamization, N-oxidation, and a highly chemoselective Grignard addition of 4-(N-tert-butylpiperidinyl)magnesium chloride to a naphthyridone N-oxide. The N-oxide exerted complete chemoselectivity via chelation in directing the Grignard addition to the alpha position as opposed to 1,4- addition on the enelactam. The dihydropyridyl adduct was in situ aromatized with isobutylchloroformate followed by heating in pyridine. Syntheses of Grignard precursor, N-tert-butyl-4-chloro-piperidine, were accomplished via transamination with a quaternary ammonium piperidone or via addition of methylmagnesium chloride to an iminium ion. Utilizing this chemistry, multi-kilogram preparation of compound 1 was successfully demonstrated.

  DOI：

  10.1021/jo061618f
• 作为产物：
  描述：

  丙烯酰氯 、 2,6-二氯苯胺 在 sodium hydroxide 作用下， 以 N,N-二甲基乙酰胺 、 水 为溶剂， 反应 2.0h， 生成 N-2,6-dichlorophenyl-acrylamide
  参考文献：
  名称：

  在不存在碱的情况下，使用亚硫酰氯在二甲基乙酰胺中直接由羧酸形成丙烯腈，丙烯酰胺和酰胺

  摘要：

  描述了一种通用的一锅法，该方法可在亚甲基乙酰胺（DMAC）中用亚硫酰氯和化学计算量的苯胺依次处理该酸时，将丙烯酸迅速转化为苯胺，产率为88-98％，而DMAC提供了速率和稳定性方面的优势。使用DMF。在形成酸酐的过程中，DMAC的使用扩展到了其他有机酸。苄胺酰胺也可以使用化学计量的苄胺形成，并在不存在其他碱的情况下通过加热使其完全。另外，显示了在20℃下添加过量的叔丁胺可以容易地形成叔丁酰胺。

  DOI：

  10.1021/op060125+

文献信息

• Formation of Acrylanilides, Acrylamides, and Amides Directly from Carboxylic Acids Using Thionyl Chloride in Dimethylacetamide in the Absence of Bases
  作者：Raymond J. Cvetovich、Lisa DiMichele

  DOI：10.1021/op060125+

  日期：2006.9.1

  one-pot procedure is described that rapidly converts acrylic acid to anilides upon sequential treatment of the acid in dimethylacetamide (DMAC) with thionyl chloride and stoichiometric amounts of anilines in 88−98% yields, with DMAC offering rate and stability advantages over the use of DMF. The use of DMAC was extended to other organic acids in forming anilides. Benzylamine amides can also be formed using

  描述了一种通用的一锅法，该方法可在亚甲基乙酰胺（DMAC）中用亚硫酰氯和化学计算量的苯胺依次处理该酸时，将丙烯酸迅速转化为苯胺，产率为88-98％，而DMAC提供了速率和稳定性方面的优势。使用DMF。在形成酸酐的过程中，DMAC的使用扩展到了其他有机酸。苄胺酰胺也可以使用化学计量的苄胺形成，并在不存在其他碱的情况下通过加热使其完全。另外，显示了在20℃下添加过量的叔丁胺可以容易地形成叔丁酰胺。
• Falbe,J.; Korte,F., Chemische Berichte, 1962, vol. 95, p. 2680 - 2687
  作者：Falbe,J.、Korte,F.

  DOI：——

  日期：——
• WO2008/53158
  申请人：——

  公开号：——

  公开（公告）日：——
• 1-2-(Pyridinyl)piperazine derivatives with antianaphylactic, antibronchospastic and mast cell stabilizing activities
  作者：Alberto Catto、Gianni Motta、Alberto Tajana、Pietro Cazzulani、Dante Nardi、Amedeo Leonardi

  DOI：10.1021/jm00384a002

  日期：1987.1

  New 1-(2-pyridinyl)piperazine derivatives were synthesized and tested as inhibitors of the reaginic passive cutaneous anaphylaxis in the rat (PCA), of the histamine-induced bronchospasm in the guinea pig, and of the rat mesenteric mast cell degranulation induced by compound 48/80. On the basis of test results, a series of N-(substituted phenyl)-omega-[4-(2-pyridinyl)-1-piperazinyl]alkanamides was prepared. The nature of substituents at the anilide ring strongly influenced mast cell stabilizing activity, whereas it was less determining in the case of the other two tests. No clear correlation between the most common physicochemical parameters (pi, sigma, Vw volume) of substituents and activity could be detected. With regard to the position of substituents at the anilide ring, the rank order of potency, in the PCA and bronchoconstriction tests, was para greater than meta greater than ortho. Introduction of substituents in the 1-(2-pyridinyl)piperazinyl moiety of the N-(substituted phenyl)propanamide derivatives hardly affected activity, or the effect was deleterious. Some of the new compounds exhibited a simultaneous remarkable activity in all the three assays employed.
• Unique Tandem Heck-Lactamization Naphthyridinone Ring Formation between Acrylanilides and Halogenated Pyridines
  作者：Raymond J. Cvetovich、Robert A. Reamer、Lisa DiMichele、John Y. L. Chung、Jennifer R. Chilenski

  DOI：10.1021/jo0613479

  日期：2006.10.1

  The Heck coupling of acrylanilides with 4-bromo-2-chloro-3-iodo-pyridine using palladium acetate can produce bis-Heck products or undergo an unusual tandem Heck-lactamization ring formation to generate 5-chloro-1-aryl-1,6-naphthyridin-2(1H)-ones.