diethyl 2-(4-oxo-1-piperidinyl)ethylphosphonate | 919835-01-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: diethyl 2-(4-oxo-1-piperidinyl)ethylphosphonate
• 英文别名: diethyl 2-(4-oxopiperidin-1-yl)ethylphosphonate；diethyl [2-(4-oxopiperidin-1-yl)ethyl]phosphonate；1-(2-diethoxyphosphorylethyl)piperidin-4-one
• CAS: 919835-01-1
• 化学式: C₁₁H₂₂NO₄P
• 分子量: 263.274
• InChiKey: UBUWRIZOQSTEHA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-吡啶甲醛 、 diethyl 2-(4-oxo-1-piperidinyl)ethylphosphonate 在 三氟化硼乙醚 作用下， 生成 BF₄^(1-)*C₂₃H₂₈N₃O₄P*H⁽¹⁺⁾
  参考文献：
  名称：

  Structure–cytotoxicity relationship in a series of N-phosphorus substituted E,E-3,5-bis(3-pyridinylmethylene)- and E,E-3,5-bis(4-pyridinylmethylene)piperid-4-ones

  摘要：

  In order to give further insight on the influence of the aromatic ring nature and the presence of the phosphorus substituent at the piperidone nitrogen atom of E,E-3,5-bis((hetero)arylidene)piperid-4-ones on their antitumor properties, a series of phosphorus substituted E,E-3,5-bis(pyridinylmethylene) piperid-4-ones bearing either 3-pyridine or 4-pyridine rings was obtained. Novel NH-3,5-bis(pyridinylmethylene)piperid-4-ones 1a,b were converted into the corresponding N-phosphorylated derivatives 3a-c, 4a-c differing in the substitution at the phosphorus atom (amidophosphates and amidophosphonates), via direct phosphorylation while N-(omega-phosphorylalkyl)-substituted compounds 8a-c were obtained via aldol-crotonic condensation of preformed N-phosphorylalkyl substituted piperidones with the corresponding pyridinecarboxaldehyde. The cytotoxicity screen has revealed that phosphorylated compounds based on E,E-3,5-bis(4-pyridinylmethylene)piperid-4-one framework displayed higher inhibitory properties toward Caov3, A549, KB 3-1 and KB 8-5 human carcinoma cell lines comparing with their analogues with 3-pyridine rings. Introduction of the phosphorus moiety substantially increased the antitumor properties in the case of E,E-3,5-bis(3-pyridinylmethylene)piperid-4-ones derivatives but this influence less pronounced for more active analogues bearing 4-pyridinyl rings. Most of the compounds tested are potent against multi-drug resistant cell line KB 8-5 affording some guidelines for the search of perspective drug-candidates among phosphorus substituted E,E-3,5-bis ((hetero)arylidene)piperid-4-ones. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.09.058
• 作为产物：
  描述：

  4-哌啶酮 、 乙烯基磷酸二乙酯 以 水 为溶剂， 反应 0.75h， 生成 diethyl 2-(4-oxo-1-piperidinyl)ethylphosphonate
  参考文献：
  名称：

  通过 Aza-Michael 反应在水中实用高效的绿色合成 β-氨基磷酰基化合物

  摘要：

  摘要 使用水作为溶剂（没有任何助溶剂）促进了乙烯基膦酸二乙酯和二苯基乙烯基氧化膦与多种 N-亲核试剂的氮杂-迈克尔反应。起始磷底物在水中的溶解度在反应过程中不起关键作用，在一定程度上降低了反应速率。该反应可以在室温或回流下进行，以通过简单的冷冻干燥分离程序以优异的产率和高纯度提供相应的 β-氨基膦酸酯和 β-氨基膦氧化物。碱性催化剂的应用使得弱亲核试剂如α-氨基酸及其磷类似物的添加成为可能；即α-氨基膦酸。

  DOI：

  10.1080/10426507.2010.511358

文献信息

• Novel 2,4-Dianilinopyrimidine Derivatives, the Preparation Thereof, Their Use as Medicaments, Pharmaceutical Compositions and, in Particular, as IKK Inhibitors
  申请人：Bosch Michael

  公开号：US20080269170A1

  公开（公告）日：2008-10-30

  The disclosure relates to compounds of formula (I): wherein R1-R5, A and Y are as defined in the disclosure, to compositions comprising said compounds, and to processes for making and methods of using the same.

  该披露涉及到式(I)的化合物：其中R1-R5、A和Y如披露中所定义，以及包含该化合物的组合物，以及制备该化合物的方法和使用该化合物的方法。
• Lewis Acids as Mild and Effective Catalysts for the Synthesis of 3,5-Bis[(hetero)arylidene]piperidin-4-ones
  作者：Evgeniya Leonova、Mihail Makarov、Zinaida Klemenkova、Irina Odinets

  DOI：10.1002/hlca.201000005

  日期：2010.10

  with (hetero)aromatic aldehydes promoted by Lewis acids or bases were examined. This comparative study has revealed three effective catalytic systems based on Lewis acids, i.e., LiClO4 and MgBr2 (in the presence of tertiary amine), and BF3⋅Et2O, for the synthesis of N‐alkyl‐substituted 3,5‐bis(heteroarylidene)piperidin‐4‐ones, including those bearing acid‐ or base‐labile groups both in the (hetero)aromatic

  考察了路易斯酸或碱促进的N-烷基和N H-哌啶-4-酮衍生物与（杂）芳族醛的醛-丁烯醛缩合反应。这个比较研究显示基于三个有效的催化系统的路易斯酸，即，的LiClO 4和MgBr 2（在叔胺的存在下），和BF 3 ⋅Et 2 O，用于合成Ñ烷基取代的3,5-双（杂亚芳基）哌啶-4-酮，包括在（杂）芳族基团和N-原子的烷基取代基中均带有酸或碱不稳定基团的那些。对于LiClO 4介导的合成，观察到最高的反应速率。既MgBr 2 -和的LiClO 4种介导的合成是低效的情况下Ñ H-哌啶-4-酮，而BF 3 ⋅Et 2 ö提供以高产率最终化合物。该催化剂特别有利，因为在O保护的哌啶-4-酮的情况下，它可以同时缩合和脱保护。
• Efficient synthesis of racemic β-aminophosphonates via aza-Michael reaction in water
  作者：Ekaterina V. Matveeva、Pavel V. Petrovskii、Irina L. Odinets

  DOI：10.1016/j.tetlet.2008.08.015

  日期：2008.10

  the addition of various amines to diethyl vinylphosphonate to yield β-aminophosphonates without any catalyst compared to known procedures for such aza-Michael reactions. The products are obtained in quantitative yields and high purity over short reaction times. Using a reactant ratio (vinylphosphonate/amine) of 2:1 resulted in double phosphorylation of primary amines.

  与用于这样的氮杂-迈克尔反应的已知方法相比，作为溶剂的水显着促进了向乙烯基膦酸二乙酯中添加各种胺，从而在没有任何催化剂的情况下产生β-氨基膦酸盐。在短的反应时间内以定量产率和高纯度获得产物。使用2：1的反应物比率（乙烯基膦酸酯/胺）导致伯胺的双重磷酸化。
• A practical and efficient green synthesis of β-aminophosphoryl compounds via the aza-Michael reaction in water
  作者：Ekaterina V. Matveeva、Pavel V. Petrovskii、Zinaida S. Klemenkova、Natalya A. Bondarenko、Irina L. Odinets

  DOI：10.1016/j.crci.2010.03.005

  日期：2010.8

  Résumé Biphasic systems room temperature imidazolium ionic liquid (RTIL)/water or water as a solvent significantly accelerate the addition of amines to vinylphosphoryl compounds hence opening green and effective synthesis of β-aminophosphoryl compounds in excellent yields over short reaction times. The application of water, being the cheapest and most non-toxic solvent, without any catalyst or co-solvent, is more advantageous as it provides a simple isolation procedure for products having high purity (> 95% according to the NMR data) via simple freeze-drying and does not require extraction with organic solvents. The solubility of the starting phosphorus substrate in water does not play crucial role in the reaction as it was demonstrated using water insoluble diphenylvinylphosphine oxide. In contrast to typical procedures, using a reactant ratio (vinylphosphoryl compound: amine) of 2:1 readily resulted in double phosphorylation of primary amines, including polyamines, in water.

  简述 室温咪唑离子液体（RTIL）/水双相体系或以水为溶剂可显著加快胺与乙烯基磷化合物的加成反应，从而在较短的反应时间内以优异的产率绿色、有效地合成β-氨基磷化合物。水是最廉价、最无毒的溶剂，不需要任何催化剂或助溶剂，因此使用水的好处更多，因为它提供了一个简单的分离程序，通过简单的冷冻干燥就能得到纯度很高（核磁共振数据显示大于 95%）的产品，而且不需要使用有机溶剂萃取。正如使用不溶于水的二苯基乙烯基氧化膦所证明的那样，起始磷底物在水中的溶解度在反应中并不起关键作用。与典型程序不同的是，使用 2:1 的反应物比例（乙烯基磷化合物：胺）很容易在水中实现伯胺（包括多胺）的双磷酸化。
• Design, cytotoxic and fluorescent properties of novel N-phosphorylalkyl substituted E,E-3,5-bis(arylidene)piperid-4-ones
  作者：Michael V. Makarov、Ekaterina Yu. Rybalkina、Gerd-Volker Röschenthaler、Kurt W. Short、Tatiana V. Timofeeva、Irina L. Odinets

  DOI：10.1016/j.ejmech.2008.10.019

  日期：2009.5

  prepared via the condensation of aromatic aldehydes with ω-aminophosphonates 5a–c and 6a,b bearing piperidone or a protected piperidone moiety, respectively. The synthetic routes to the starting aminophosphonates 5a–c and 6a,b varied depending on the number of methylene groups in the alkylene chain and comprised the Kabachnik–Fields reaction (n = 1), the aza-Michael reaction (n = 2) or alkylation of 4-piperidone

  通过芳族醛与ω-氨基膦酸酯5a - c和6a，b带有哌啶酮或a的缩合反应，制得一系列E，E - N-磷酰基亚烷基-3,5-双（亚芳基）哌啶-4-酮7a - k。保护的哌啶酮部分。起始氨基膦酸酯5a – c和6a，b的合成路线因亚烷基链中亚甲基的数量而异，包括Kabachnik-Fields反应（n  = 1），aza-Michael反应（n ＝ 2）或在相转移催化条件下用ω-溴代烷基膦酸二乙酯将4-哌啶酮盐酸盐烷基化（n  ＝ 3，4）。芳基环对位上带有硝基和氟原子的磷酰基取代的3,5-双（亚芳基）哌啶-4-酮7b，c，e，f，h，i，k对人癌细胞具有细胞毒性低摩尔浓度的CaOv3，Scov3，PC3和A549系，而其具有对二甲氨基的类似物的IC 50值大于50μM。相比之下，只有我2N-取代的膦酸酯7g，j（n  ＝ 3和4）和Me 2 N-取代的膦酸10c，f（n  ＝ 2和3）的盐显示荧光。