ethyl 1-p-tolyl-6-oxo-5-cyano-4-methyl-1,6-dihydropyridazine-3-carboxylate | 125040-80-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: ethyl 1-p-tolyl-6-oxo-5-cyano-4-methyl-1,6-dihydropyridazine-3-carboxylate
• 英文别名: ethyl-5-cyano-1,6-dihydro-4-methyl-6-oxo-1-(4-tolyl)-3-pyridazinecarboxylate；ethyl 5-cyano-4-methyl-1-(p-tolyl)-6-oxo-1,6-dihydropyridazine-3-carboxylate；ethyl 5-cyano-4-methyl-6-oxo-1-(p-tolyl)-1,6-dihydropyridazine-3-carboxylate；ethyl 5-cyano-1,6-dihydro-4-methyl-6-oxo-1-p-tolylpyridazine-3-carboxylate；ethyl 5-cyano-4-methyl-1-(4-methylphenyl)-6-oxopyridazine-3-carboxylate
• CAS: 125040-80-4
• 化学式: C₁₆H₁₅N₃O₃
• 分子量: 297.313
• InChiKey: RARYEMAPYRVANE-UHFFFAOYSA-N

物化性质

• 熔点：
  164 °C(Solvent: Ethanol)
• 沸点：
  431.9±55.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  82.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 1-p-tolyl-6-oxo-5-cyano-4-methyl-1,6-dihydropyridazine-3-carboxylate 在 盐酸 、 溶剂黄146 作用下， 反应 2.0h， 以76.9%的产率得到5-cyano-6-oxo-4-methyl-1-p-tolylpyridazinium-3-carboxylate
  参考文献：
  名称：

  Elnagdi, Mohamed Hilmy; Erian, Ayman Wahba; Sadek, Kamal Usef, Journal of Chemical Research, Miniprint, 1990, # 5, p. 1124 - 1142

  摘要：

  DOI：
• 作为产物：
  描述：

  ethyl 2-(4-tolyl)hydrazono-3-oxobutyrate 、 氰乙酸乙酯 在 乙酸铵 作用下， 以 溶剂黄146 、 苯 为溶剂， 反应 7.0h， 以82%的产率得到ethyl 1-p-tolyl-6-oxo-5-cyano-4-methyl-1,6-dihydropyridazine-3-carboxylate
  参考文献：
  名称：

  Elnagdi, Mohamed Hilmy; Aal, Fatma Abdel Maksoud Abdel; Hafez, Ebtisam Abdel Aziz, Zeitschrift fur Naturforschung, B: Chemical Sciences, 1989, vol. 44, # 6, p. 683 - 689

  摘要：

  DOI：

文献信息

• Studies on Polyfunctionalised Heteroaromatics: Synthesis of Several New Cinnoline and Pyrido[3,4-c]pyridazine Derivatives
  作者：Magda A. Barsy

  DOI：10.1002/jccs.200000131

  日期：2000.8

  One-pot reaction of ethyl 2-aryhydrazono-3-oxobutyrates with cyanoacetamide afforded pyridazine and pyridine derivatives, which were found to be excellent precursors for the synthesis of different cinnolines and pyrido[3,4-c]pyridazines, respectively.

  2-aryhydrazono-3-oxobutyrate 乙酯与氰基乙酰胺的一锅反应得到哒嗪和吡啶衍生物，发现它们分别是合成不同的 cinnolines 和 pyrido[3,4-c] 哒嗪的优良前体。
• Green and efficient synthesis of polyfunctionally substituted cinnolines under controlled microwave irradiation
  作者：Afaf Abdel Hameed、Essam Khalaf Ahmed、Asmaa A. Abdel Fattah、Carlos Kleber Z. Andrade、Kamal Usef Sadek

  DOI：10.1007/s11164-017-2944-1

  日期：2017.10

  Abstract A convenient, simple and efficient synthesis of polyfunctionally substituted cinnolines has been developed that involves the reaction of ethyl 5-cyano-4-methyl-1-aryl-6-oxo-1,6-dihydropyridazine-3-carboxylate with nitroolefins in dioxane/piperidine under controlled microwave irradiation. The obtained heterocycles are a privileged scaffold in a few natural compounds and in many drugs with a

  摘要 已经开发了一种方便，简单且有效的多官能取代肉桂酸合成方法，该方法涉及在氰基/二恶烷中使5-氰基-4-甲基-1-甲基-1-芳基-6-氧代-1,6-二氢哒嗪-3-羧酸乙酯与硝基烯烃反应。哌啶在受控微波辐射下。所获得的杂环是一些天然化合物和具有广泛生物活性的许多药物中的特权支架。 图形概要
• Enamines in Heterocyclic Synthesis: A Novel Simple and Efficient Route to Condensed Pyridazines
  作者：Elham S. Darwish、Mahmoud A. Abdelrahman、Abdellatif M. Salaheldin

  DOI：10.1515/znb-2011-0607

  日期：2011.6.1

  An efficient and easy preparation of enamine derivatives, via active methyl and methylene compounds by in situ-generated 1-(diethoxymethyl)piperidine, produced from the mixture of triethyl orthoformate/piperidine/DMF, are described. Some new pyridazinone derivatives have been synthesized from the reaction of enamines with hydrazine hydrate and cyanoacid hydrazide. Graphical Abstract Enamines in Heterocyclic

  描述了通过原位生成的 1-（二乙氧基甲基）哌啶通过活性甲基和亚甲基化合物有效且容易地制备烯胺衍生物，该化合物由原甲酸三乙酯/哌啶/DMF 的混合物产生。一些新的哒嗪酮衍生物由烯胺与水合肼和氰基酰肼反应合成。杂环合成中的图形抽象烯胺：一种新的简单有效的缩合哒嗪途径
• Synthesis of Polyfunctional Pyridazine Derivatives Using a Solvent-Free Microwave Assisted Method
  作者：Eddy Sotelo、Raúl Mocelo、Margarita Suárez、André Loupy

  DOI：10.1080/00397919708004105

  日期：1997.7

  Abstract The synthesis of several polyfunctional pyridazine derivatives has been carried out very efficiently under microwave irradiation and solvent-free conditions allowing short reaction times and high yields. Non thermal effects induced by microwave were observed.

  摘要 几种多功能哒嗪衍生物的合成在微波辐射和无溶剂条件下进行，反应时间短，收率高。观察到由微波引起的非热效应。
• Controlled microwave-assisted reactions: A facile synthesis of polyfunctionally substituted phthalazines as dual EGFR and PI3K inhibitors in CNS SNB-75 cell line
  作者：Maiiada Hassan Nazmy、Ramadan Ahmed Mekheimer、Mai E. Shoman、Mohamed Abo-Elsebaa、Mohamed Abd-Elmonem、Kamal Usef Sadek

  DOI：10.1016/j.bioorg.2022.105740

  日期：2022.5

  particular cell line, CNS SNB-75 cell line, but (5b) exhibited the highest growth inhibitory activity against CNS-SNB-75 cell line with (GI% = 108.81) and (IC50 = 3.703 ± 0.2) compared to erlotinib; (IC50 = 12.5 ± 0.68). It caused Pre-G1 apoptosis and growth arrest at S phase. It also increased percentage of the total apoptotic cells in CNS-SNB-75 cell line (39.26%) compared to control cells (2.17%)

  脑肿瘤是顽固的癌症，预后差，存活率令人失望。迫切需要具有更高疗效和更低耐药性的靶向癌症治疗药物。通过将 1-aryl-5-cyano-1,6-dihydro-4-methyl-6-oxo-3-pyridazine-carboxylate 与肉桂腈衍生物的环加成反应，开发了一种高效的多官能化酞嗪衍生物的一锅法合成方法。噻吩并[3,4- d ]哒嗪在受控微波加热下具有高产率的活化双键或三键系统。合成的酞嗪类化合物（5a-e、9和13 ）通过体外试验测试了它们的体外抗癌活性。美国国家癌症研究所的一次剂量测定。只有酞嗪(5b ) 对来自所有子组的大多数测试癌细胞系显示出广谱抗肿瘤活性，平均 % GI = 22.61。有趣的是，所有测试的化合物都对特定细胞系 CNS SNB-75 细胞系表现出不同的生长抑制活性，但 ( 5b ) 对 CNS-SNB-75 细胞系表现出最高的生长抑制活性 (GI% =