5-chloro-1-(2,6-dichlorophenyl)-1,6-naphthyridin-2(1H)-one | 916203-59-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 5-chloro-1-(2,6-dichlorophenyl)-1,6-naphthyridin-2(1H)-one
• 英文别名: 5-chloro-1-(2,6-dichlorophenyl)-1,6-naphthyridin-2-one
• CAS: 916203-59-3
• 化学式: C₁₄H₇Cl₃N₂O
• 分子量: 325.581
• InChiKey: GGHODCIXVZGKEE-UHFFFAOYSA-N

物化性质

• 沸点：
  495.4±45.0 °C(Predicted)
• 密度：
  1.547±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  5-chloro-1-(2,6-dichlorophenyl)-1,6-naphthyridin-2(1H)-one 在 potassium chloride 、 palladium diacetate 四丁基溴化铵 、 sodium carbonate 、 间氯过氧苯甲酸 、 三苯基膦 作用下， 以 水 、 甲苯 为溶剂， 反应 24.0h， 生成
  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：

  2-氯-4-溴吡啶 在 palladium diacetate sodium acetate 、 potassium bromide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 7.0h， 生成 5-chloro-1-(2,6-dichlorophenyl)-1,6-naphthyridin-2(1H)-one
  参考文献：
  名称：

  Unique Tandem Heck-Lactamization Naphthyridinone Ring Formation between Acrylanilides and Halogenated Pyridines

  摘要：

  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.

  DOI：

  10.1021/jo0613479

文献信息

• 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.
• Synthesis of a Naphthyridone p38 MAP Kinase Inhibitor
  作者：John Y. L. Chung、Raymond J. Cvetovich、Mark McLaughlin、Joseph Amato、Fuh-Rong Tsay、Mark Jensen、Steve Weissman、Daniel Zewge

  DOI：10.1021/jo061618f

  日期：2006.10.1

  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.