1-(4-methoxybenzyl)-4-methylpiperidine-2,6-dione | 566151-57-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(4-methoxybenzyl)-4-methylpiperidine-2,6-dione
• 英文别名: 1-[(4-Methoxyphenyl)methyl]-4-methylpiperidine-2,6-dione
• CAS: 566151-57-3
• 化学式: C₁₄H₁₇NO₃
• 分子量: 247.294
• InChiKey: RNQLQRUTSUWAMK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-methoxybenzyl)-4-methylpiperidine-2,6-dione 在 二异丁基氢化铝 、 甲基磺酰氯 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 3.0h， 生成 1-(4-methoxybenzyl)-4-methyl-3,4-dihydropyridin-2-one
  参考文献：
  名称：

  通过立体选择性环丙烷化反应合成 2-氮杂双环 [4.1.0] 庚烷

  摘要：

  在金属配合物催化的重氮化合物分解的帮助下，不饱和δ-内酰胺被环丙烷化。报道了对反应条件、立体化学结果和基团保护的研究。所得双环产物与生物活性化合物有关。转化为硫内酰胺有利于分离获得的不同异构体和去除保护基团。环丙烷化反应适用于多种重氮化合物。

  DOI：

  10.1002/ejoc.201000863
• 作为产物：
  描述：

  3-甲基戊二酸酐 在 乙酸酐 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 生成 1-(4-methoxybenzyl)-4-methylpiperidine-2,6-dione
  参考文献：
  名称：

  设计和合成诱导型一氧化氮合酶的抑制剂。发现一种具有潜在口服生物利用度的新化学铅。

  摘要：

  合成了一系列与小成员环稠合的2-亚氨基哌啶（表1和表2），并使用体外人一氧化氮合酶（NOS）抑制试验进行了生物学评估。融合的双环化合物5-9在hiNOS抑制试验中显示出与化合物1几乎相同的效价。其中，1-甲基类似物8​​和9分别显示出比其相应的未取代类似物7和6更好的同工型选择性。还通过小鼠模型中的体内NO累积测定法评估了化合物5和6。报道了口服生物利用型人诱导型NOS（iNOS）抑制剂的新化学线索的发现过程。还报道了这些化合物的结构-活性关系（SAR）研究和化学性质。

  DOI：

  10.1016/s0223-5234(03)00017-5

文献信息

• General Approach to Nitrogen-Bridged Bicyclic Frameworks by Rh-Catalyzed Formal Carbenoid Insertion into an Amide C–N Bond
  作者：Shingo Harada、Masato Kono、Tomoyuki Nozaki、Yasuhiro Menjo、Tetsuhiro Nemoto、Yasumasa Hamada

  DOI：10.1021/acs.joc.5b01954

  日期：2015.10.16

  Various nitrogen-bridged bicyclic skeletons are found in bioactive natural products and pharmaceuticals. The development of a new reaction to construct these molecular frameworks has attracted considerable attention in synthetic organic chemistry. We developed a novel synthetic method for obtaining a wide variety of nitrogen-bridged bicyclic compounds with a catalytic process, Rh-catalyzed formal carbenoid insertion into an amide C-N bond. Using 0.1-0.4 mol % Rh-2((NHCOBu)-Bu-t)(4) catalyst, various azabicydo[X.Y.Z]alkane derivatives were obtained in good to excellent yield, successfully demonstrating the broad substrate scope of the developed process. Experimental and computational studies to elucidate the reaction mechanism revealed that the formal insertion reaction of a carbenoid into an amide C-N bond proceeded via the formation of Rh-associated N-ylides, followed by an acyl group-selective Stevens [1,2]-shift through a concerted addition/elimination process on the sp(2)-hybridized carbon.
• Design and Synthesis of Orally Bioavailable Inhibitors of Inducible Nitric Oxide Synthase. Identification of 2-Azabicyclo[4.1.0]heptan-3-imines
  作者：Yasufumi Kawanaka、Kaoru Kobayashi、Shinya Kusuda、Tadashi Tatsumi、Masayuki Murota、Toshihiko Nishiyama、Katsuya Hisaichi、Atsuko Fujii、Keisuke Hirai、Masao Naka、Masaharu Komeno、Yshihiko Odagaki、Hisao Nakai、Masaaki Toda

  DOI：10.1016/s0968-0896(03)00034-8

  日期：2003.4

  Further chemical modification of 2-iminopiperidines fused to cyclopropane rings was performed. Optically active isomers 2 and 13 were synthesized and their biological activity was evaluated. Compound 2 exhibited greater potency and more isoform selectivity than enantiomer 13 in the iNOS inhibition assay. One of the gem-chlorines on the fused cyclopropane moiety of 2 was eliminated to produce 3, which showed reduced potency for iNOS inhibition, as well as 4 with an increased potency. The isoform selectivity of 4 was also much higher than that of 3. This was also true for the corresponding methyl derivatives 6-9. The structure-activity relationship (SAR) study and computer aided docking study of the most optimized structure 4 with human iNOS will also be reported. (C) 2003 Elsevier Science Ltd. All rights reserved.
• Synthesis of 2-Azabicyclo[4.1.0]heptanes through Stereoselective Cyclopropanation Reactions
  作者：Irene Suárez del Villar、Ana Gradillas、Javier Pérez-Castells

  DOI：10.1002/ejoc.201000863

  日期：2010.10

  catalysed by metal complexes. A study of the reaction conditions, stereochemical outcome and group protection is reported. The resulting bicyclic products are related to bioactive compounds. Transformation into thiolactams facilitates the separation of the different isomers obtained and the removal of the protecting group. The cyclopropanation reaction works with diverse diazo compounds.

  在金属配合物催化的重氮化合物分解的帮助下，不饱和δ-内酰胺被环丙烷化。报道了对反应条件、立体化学结果和基团保护的研究。所得双环产物与生物活性化合物有关。转化为硫内酰胺有利于分离获得的不同异构体和去除保护基团。环丙烷化反应适用于多种重氮化合物。
• Design and synthesis of inhibitors of inducible nitric oxide synthase. Discovery of a new chemical lead with potential for oral bioavailability
  作者：Yasufumi Kawanaka、Kaoru Kobayashi、Shinya Kusuda、Tadashi Tatsumi、Masayuki Murota、Toshihiko Nishiyama、Katsuya Hisaichi、Atsuko Fujii、Keisuke Hirai、Masao Naka、Masaharu Komeno、Hisao Nakai、Masaaki Toda

  DOI：10.1016/s0223-5234(03)00017-5

  日期：2003.3

  A series of 2-iminopiperidines fused to small-membered rings (Tables 1 and 2) were synthesised and biologically evaluated using an in vitro human nitric oxide synthase (NOS) inhibition assay. Fused bicyclic compounds 5-9 exhibited nearly the same potency as compound 1 in the hiNOS inhibition assay. Among these, the 1-methyl analogues 8 and 9 showed better isoform selectivity than their corresponding

  合成了一系列与小成员环稠合的2-亚氨基哌啶（表1和表2），并使用体外人一氧化氮合酶（NOS）抑制试验进行了生物学评估。融合的双环化合物5-9在hiNOS抑制试验中显示出与化合物1几乎相同的效价。其中，1-甲基类似物8​​和9分别显示出比其相应的未取代类似物7和6更好的同工型选择性。还通过小鼠模型中的体内NO累积测定法评估了化合物5和6。报道了口服生物利用型人诱导型NOS（iNOS）抑制剂的新化学线索的发现过程。还报道了这些化合物的结构-活性关系（SAR）研究和化学性质。