3-amino-1-(2-methylphenyl)-5,10-dihydro-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile | 1417454-83-1

• 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: 3-amino-1-(2-methylphenyl)-5,10-dihydro-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile
• 英文别名: 3-Amino-1-(2-methylphenyl)-5,10-dioxo-5,10-dihydro-1h-pyrazolo[1,2-b]phthalazine-2-carbonitrile；3-amino-1-(2-methylphenyl)-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile
• CAS: 1417454-83-1
• 化学式: C₁₉H₁₄N₄O₂
• 分子量: 330.346
• InChiKey: ZECGNNBBSDPQHL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  25
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  90.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-amino-1-(2-methylphenyl)-5,10-dihydro-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile 、 环己酮 在 aluminum (III) chloride 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 24.0h， 以90%的产率得到15-amino-14-(o-tolyl)-2,3,4,14-tetrahydro-1H-quinolino[2',3':3,4]pyrazolo[1,2-b]phthalazine-7,12-dione
  参考文献：
  名称：

  New racemic annulated pyrazolo[1,2-b]phthalazines as tacrine-like AChE inhibitors with potential use in Alzheimer's disease

  摘要：

  A novel series of tacrine-like compounds 7a-u possessing a fused pyrazolo[1,2-b]phthalazine structure were designed and synthesized as potent and selective inhibitors of AChE. The in-vitro biological assessments demonstrated that several compounds had high anti-AChE activity at nano-molar level. The more promising compound 71 with IC50 of 49 nM was 7-fold more potent than tacrine and unlike tacrine, it was highly selective against AChE over BuChE. The cell-based assays against hepatocytes (HepG2) and neuronal cell line (PC12) revealed that 71 had significantly lower hepatotoxicity compared to tacrine, with additional neuroprotective activity against H2O2-induced damage in PC12 cells. This compound could also inhibit AChE-induced and self-induced A beta peptide aggregation. The advantages including synthetic accessibility, high potency and selectivity, low toxicity, adjunctive neuroprotective and A beta aggregation inhibitory activity, make this compound as a new multifunctional lead for Alzheimer's disease drug discovery. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.07.072
• 作为产物：
  描述：

  苯酐 在 一水合肼 作用下， 反应 0.17h， 生成 3-amino-1-(2-methylphenyl)-5,10-dihydro-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile
  参考文献：
  名称：

  温和的碱性离子液体催化1 H-吡唑并[1,2-b]酞嗪-5,10-二酮的新四组分合成

  摘要：

  使用三种弱碱性离子液体，例如1,8-二氮杂双环[5.4.0] -undec-7-en，由1 H-吡唑并[1,2-b]酞嗪-5,10-二酮衍生物组成的新的四组分合成方法描述了在环境温度和无溶剂条件下，一水合肼，邻苯二甲酸酐，丙二腈或氰基乙酸乙酯与芳族醛的缩合反应的高效催化剂，乙酸-8-铵，甲酸吡咯烷鎓盐和乙酸吡咯烷鎓盐具有优异的收率。

  DOI：

  10.1016/j.molliq.2012.06.007

文献信息

• Mild preparation of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives with magnetic Fe3O4 nanoparticles coated by (3-aminopropyl)-triethoxysilane as catalyst under ambient and solvent-free conditions
  作者：Hamid Reza Shaterian、Majid Mohammadnia

  DOI：10.1007/s11164-012-0969-z

  日期：2014.1

  An efficient, one-pot quantitative procedure for preparation of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives from four-component condensation reaction of hydrazine monohydrate, phthalic anhydride, malononitrile or ethyl cyanoacetate, and aromatic aldehydes in the presence of magnetic Fe3O4 nanoparticles coated by (3-aminopropyl)-triethoxysilane as catalyst under mild, ambient, and solvent-free conditions is described. Simple procedure, high yield, short reaction time, and environmentally benign method are advantages of this protocol. The magnetic Fe3O4 nanoparticles coated by (3-aminopropyl)-triethoxysilane can be recovered and reused several times without loss of activity.

  描述了一种高效的一锅法定量制备1H-吡唑并[1,2-b]酞嗪-5,10-二酮衍生物的方法，该方法通过水合肼、邻苯二甲酸酐、丙二腈或氰乙酸乙酯与芳香醛在磁性Fe3O4纳米粒子（表面包覆有(3-氨丙基)-三乙氧基硅烷）催化下进行四组分缩合反应，条件温和、环境、无溶剂。该方案的优点是操作简单、产率高、反应时间短、环境友好。磁性 纳米粒子（表面包覆有(3-氨丙基)-三乙氧基硅烷）可回收并重复使用多次而不会丧失活性。
• Preparation of 1<i>H</i>-pyrazolo[1,2-<i>b</i>]phthalazine-5,10-diones using ZrO₂ nanoparticles as a catalyst under solvent-free conditions
  作者：Mohammad Piltan

  DOI：10.1515/hc-2017-0142

  日期：2017.10.26

  Abstract Zirconium oxide nanoparticles are an efficient catalyst for the preparation of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones via a three-component reaction of phthalhydrazide, aromatic aldehydes and malononitrile under solvent-free conditions.

  摘要 氧化锆纳米颗粒是一种有效的催化剂，可在无溶剂条件下通过邻苯二甲酰肼、芳香醛和丙二腈的三组分反应制备 1H-吡唑并[1,2-b]酞嗪-5,10-二酮。
• New role for photoexcited organic dye, Na2 eosin Y via the direct hydrogen atom transfer (HAT) process in photochemical visible-light-induced synthesis of spiroacenaphthylenes and 1H-pyrazolo[1,2-b]phthalazine-5,10-diones under air atmosphere
  作者：Farzaneh Mohamadpour

  DOI：10.1016/j.dyepig.2021.109628

  日期：2021.10

  A green multi-component tandem strategy for metal-free synthesizing spiroacenaphthylenes and 1H-pyrazolo[1,2-b]phthalazine-5,10-diones by Knoevenagel-Michael cyclocondensation is reported via organic dye Na2 eosin Y-derived photoexcited states functions as a direct hydrogen atom transfer (HAT) catalyst via visible light-mediated in aqueous ethyl lactate at ambient temperature under air atmosphere.

  通过有机染料 Na 2曙红 Y 衍生的光激发态，通过Knoevenagel-Michael 环缩合反应无金属合成螺苊和 1 H-吡唑并[1,2 - b ]酞嗪-5,10-二酮的绿色多组分串联策略在环境温度和空气气氛下，通过可见光介导的乳酸乙酯水溶液作为直接氢原子转移 (HAT) 催化剂。这项研究为进一步使用具有商业可用性和廉价性的无金属有机染料 Na 2曙红Y在光化学合成中使用最少的催化剂，能源效率高，收率高，操作简单，反应省时，原子经济性高，从而满足可持续和绿色化学的一些特征。值得注意的是，这种环化反应也可以在克级规模上运行，这凸显了该反应在工业用途中的潜力。
• DMAP as a new efficient catalyst for the one-pot synthesis of condensed phthalazines
  作者：Esma Lamera、Sofiane Bouacida、Hocine Merazig、Aissa Chibani、Marc Le Borgne、Zouhair Bouaziz、Abdelmalek Bouraiou

  DOI：10.1515/znb-2016-0262

  日期：2017.5.1

  Abstract A new, convenient, and efficient method for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones is developed starting from phthalhydrazide, aromatic aldehydes, and malononitrile using 4-N,N-dimethylaminopyridin as catalyst. This modified route provides much higher yields and a simple work-up procedure of products. Also this methodology is of interest due to the use of ethanol as a solvent

  摘要 以邻苯二甲酰肼、芳香醛和丙二腈为原料，以 4-N,N-二甲氨基吡啶为原料，开发了一种简便高效的合成 1H-吡唑并[1,2-b]酞嗪-5,10-二酮的方法。催化剂。这种改进的路线提供了更高的产率和简单的产品后处理程序。此外，由于使用乙醇作为溶剂而不使用任何有毒金属作为催化剂，因此这种方法很有趣，从而最大限度地降低了成本、操作危害和环境污染。
• Experimental and DFT mechanistic insights into one-pot synthesis of 1<i>H</i>-pyrazolo[1,2-<i>b</i>]phthalazine-5,10-diones under catalysis of DBU-based ionic liquids
  作者：Sara Fallah-Ghasemi Gildeh、Morteza Mehrdad、Hossein Roohi、Khatereh Ghauri、Sahar Fallah-Ghasemi Gildeh、Kurosh Rad-Moghadam

  DOI：10.1039/d0nj03478a

  日期：——

  Benzylation of DBU followed by anion exchange of the resulting salt with trifluoroacetate gave nearly quantitatively the ionic liquid [Bn-DBU][TFA]. It is shown here to be an efficient catalyst for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones via the three-component reaction of phthalhydrazide, aromatic aldehydes, and active α-methylene nitriles. DFT calculations at the B3LYP/SVP level and the

  DBU的苯甲酰化，然后将所得盐与三氟乙酸根阴离子交换，几乎定量地得到了离子液体[Bn-DBU] [TFA]。在此显示出对于1合成的有效催化剂ħ -吡唑并[1,2- b ]酞嗪-5,10-二酮通过邻苯二甲酰肼，芳族醛和活性α-亚甲基腈的三组分反应。在B3LYP / SVP级别的DFT计算和实验结果与该反应的三步机理一致。基于DFT计算，催化效果很大程度上来自离子液体的固有离子性质，而不是其作为简单碱的作用。这些计算还预测了两种近能量活化的络合物的存在，它们的速率决定作用和能量取决于它们与离子液体中阴离子组分的相互作用，因为[Bn-DBU] [TFA]的催化活性高于[Bn-DBU] [OAc]。这种机理学方法为合成1 H的离子液体催化剂的合理设计开辟了新的和有希望的见解。-吡唑并[1,2 - b ]酞嗪-5,10-二酮。这里介绍的合成方法具有几个突出的优点。