4,6-ditert-butyl-1H-pyridin-2-one | 1416332-45-0

• 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: 4,6-ditert-butyl-1H-pyridin-2-one
• CAS: 1416332-45-0
• 化学式: C₁₃H₂₁NO
• 分子量: 207.316
• InChiKey: CJJUZCFCSXYZFN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 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：

  4,6-ditert-butyl-1H-pyridin-2-one 在 copper(l) iodide 、 potassium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 50.0h， 生成
  参考文献：
  名称：

  Effects of Hindrance in N-Pyridyl Imidazolylidenes Coordinated to Iridium on Structure and Catalysis

  摘要：

  The unhindered N-pyrid-2-yl imidazolidene NHC ligand has been shown to chelate to a Cp*Ir fragment (1). With the goal of weakening the coordination of the pyridyl substituent and enabling its role as pendant base or hemilabile ligand, a tert-butyl group at C-6 next to the pyridyl N was installed. Attempted coordination of the newly synthesized carbene ligand avoided N-coordination entirely, but led to unexpected C-metalation at C-3 by the Cp*Ir center. Successful formation of a weakly N-coordinated analogue was achieved by synthesizing a ligand with a second tert-butyl group at C-4. The complexes were studied using X-ray crystallography and NMR spectroscopy. The X-ray crystal structure of di-tert-butyl analogue 6 showed that in the solid the complex existed as a chloride-bridged dimer, with the pyridyl nitrogen uncoordinated. In solution, N-15 chemical shift information revealed that 6 existed with the pyridyl substituent N-coordinated, presumably as a monomer, but that addition of an amine ligand readily opened the chelate. Finally, 6 was used as a catalyst for intramolecular hydroamination of primary and secondary alkenylamines. Comparing (heteroaryl)NHC species, each with a tert-butyl group next to the nitrogen, which enables hydroamination, the rate differences are very modest but increase in the order imidazolyl < pyridyl < pyrimidyl, which may be an effect of basicity but because of the similarity in rates is better ascribed to counterbalancing of more than one factor, including hemilability. The (4,6-di-tert-butyl)pyridyl species 6 was shown to be much more effective compared to parent compound 1 without the tert-butyl groups, in which the chelating group was more tightly bound.

  DOI：

  10.1021/om400758b
• 作为产物：
  描述：

  4,6-di-tert-butyl-3-(methoxycarbonyl)-2H-pyran-2-one 以 1,4-二氧六环 为溶剂， 反应 4.3h， 生成 4,6-ditert-butyl-1H-pyridin-2-one
  参考文献：
  名称：

  Effects of Hindrance in N-Pyridyl Imidazolylidenes Coordinated to Iridium on Structure and Catalysis

  摘要：

  The unhindered N-pyrid-2-yl imidazolidene NHC ligand has been shown to chelate to a Cp*Ir fragment (1). With the goal of weakening the coordination of the pyridyl substituent and enabling its role as pendant base or hemilabile ligand, a tert-butyl group at C-6 next to the pyridyl N was installed. Attempted coordination of the newly synthesized carbene ligand avoided N-coordination entirely, but led to unexpected C-metalation at C-3 by the Cp*Ir center. Successful formation of a weakly N-coordinated analogue was achieved by synthesizing a ligand with a second tert-butyl group at C-4. The complexes were studied using X-ray crystallography and NMR spectroscopy. The X-ray crystal structure of di-tert-butyl analogue 6 showed that in the solid the complex existed as a chloride-bridged dimer, with the pyridyl nitrogen uncoordinated. In solution, N-15 chemical shift information revealed that 6 existed with the pyridyl substituent N-coordinated, presumably as a monomer, but that addition of an amine ligand readily opened the chelate. Finally, 6 was used as a catalyst for intramolecular hydroamination of primary and secondary alkenylamines. Comparing (heteroaryl)NHC species, each with a tert-butyl group next to the nitrogen, which enables hydroamination, the rate differences are very modest but increase in the order imidazolyl < pyridyl < pyrimidyl, which may be an effect of basicity but because of the similarity in rates is better ascribed to counterbalancing of more than one factor, including hemilability. The (4,6-di-tert-butyl)pyridyl species 6 was shown to be much more effective compared to parent compound 1 without the tert-butyl groups, in which the chelating group was more tightly bound.

  DOI：

  10.1021/om400758b

文献信息

• 2-Pyridone Synthesis Using 2-(Phenylsulfinyl)acetamide
  作者：Masaya Fujii、Takuya Nishimura、Takahiro Koshiba、Satoshi Yokoshima、Tohru Fukuyama

  DOI：10.1021/ol303320c

  日期：2013.1.4

  2-Pyridones were prepared by means of an efficient protocol including the 1,4-addition of 2-(phenylsulfinyl)acetamide to α,β-unsaturated ketones followed by cyclization and sulfoxide elimination.

  通过有效的方法制备2-吡啶酮，包括将2-（苯基亚磺酰基）乙酰胺的1,4-加成到α，β-不饱和酮上，然后环化和消除亚砜。
• MACROCYCLES AS FACTOR XIA INHIBITORS
  申请人：Corte James R.

  公开号：US20120041190A1

  公开（公告）日：2012-02-16

  The present invention provides compounds of Formula (I): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein all the variables are as defined herein. These compounds are selective Factor XIa inhibitors or dual inhibitors of fXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

  本发明提供了式(I)的化合物：或其立体异构体、互变异构体或药学上可接受的盐，其中所有变量如此定义。这些化合物是选择性因子XIa抑制剂或fXIa和血浆卡利肌酶的双重抑制剂。本发明还涉及包含这些化合物的制药组合物以及使用它们治疗血栓栓塞和/或炎症性疾病的方法。
• DIHYDROPYRIDONE P1 AS FACTOR XIA INHIBITORS
  申请人：Bristol-Myers Squibb Company

  公开号：US20140038969A1

  公开（公告）日：2014-02-06

  The present invention provides compounds of Formula (VIII): or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

  本发明提供公式（VIII）的化合物：或其立体异构体，互变异构体或药学上可接受的盐，其中所有变量如本文所定义。这些化合物是选择性因子XIa抑制剂或FXIa和血浆卡利肽酶的双重抑制剂。本发明还涉及包含这些化合物的制药组合物和使用它们治疗血栓栓塞性和/或炎症性疾病的方法。
• CYCLIC P1 LINKERS AS FACTOR XIA INHIBITORS
  申请人：Lam Patrick Y.S.

  公开号：US20140163002A1

  公开（公告）日：2014-06-12

  The present invention provides compounds of Formula (Ia): or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

  本发明提供了式(Ia)的化合物：或其立体异构体、互变异构体或药学上可接受的盐，其中所有变量如本文所定义。这些化合物是选择性因子XIa抑制剂或FXIa和血浆卡利肯双重抑制剂。本发明还涉及包含这些化合物的制药组合物以及使用它们治疗血栓栓塞性和/或炎症性疾病的方法。
• NOVEL MACROCYCLES AS FACTOR XIA INHIBITORS
  申请人：Pinto Donald J. P.

  公开号：US20140221338A1

  公开（公告）日：2014-08-07

  The present invention provides compounds of Formula (Ia): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

  本发明提供以下式（Ia）的化合物：或其立体异构体、互变异构体或药学上可接受的盐，其中所有变量均如本文所定义。这些化合物是选择性因子XIa抑制剂或FXIa和血浆卡利肌酶的双重抑制剂。本发明还涉及包含这些化合物的药物组合物以及使用它们治疗血栓栓塞性和/或炎症性疾病的方法。