6-amino-4-(2,6-dichlorophenyl)-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile | 879589-69-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-amino-4-(2,6-dichlorophenyl)-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile
• 英文别名: 6-amino-3-methyl-4-(2,6-dichlorophenyl)-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile；6-Amino-4-(2,6-dichlorophenyl)-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile
• CAS: 879589-69-2
• 化学式: C₁₄H₁₀Cl₂N₄O
• 分子量: 321.166
• InChiKey: LWGHDZDVLKSUSC-UHFFFAOYSA-N

物化性质

• 熔点：
  249-250 °C(Solv: ethanol (64-17-5))
• 沸点：
  544.9±50.0 °C(Predicted)
• 密度：
  1.57±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  87.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-甲基-3-吡唑啉-5-酮 、 2,6-二氯苯亚甲基丙二腈 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.03h， 以64%的产率得到6-amino-4-(2,6-dichlorophenyl)-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile
  参考文献：
  名称：

  Dihydropyrano [2,3-c] pyrazole: Novel in vitro inhibitors of yeast α-glucosidase

  摘要：

  Inhibition of alpha-glucosidase enzyme activity is a reliable approach towards controlling post-prandial hyperglycemia associated risk factors. During the current study, a series of dihydropyrano[ 2,3-c] pyrazoles (1-35) were synthesized and evaluated for their a-glucosidase inhibitory activity. Compounds 1, 4, 22, 30, and 33 were found to be the potent inhibitors of the yeast alpha-glucosidase enzyme. Mechanistic studies on most potent compounds reveled that 1, 4, and 30 were non-competitive inhibitors (K-i = 9.75 +/- 0.07, 46 +/- 0.0001, and 69.16 +/- 0.01 mu M, respectively), compound 22 is a competitive inhibitor (K-i = 190 +/- 0.016 mu M), while 33 was an uncompetitive inhibitor (K-i = 45 +/- 0.0014 mu M) of the enzyme. Finally, the cytotoxicity of potent compounds (i.e. compounds 1, 4, 22, 30, and 33) was also evaluated against mouse fibroblast 3T3 cell line assay, and no toxicity was observed. This study identifies non-cytotoxic novel inhibitors of alpha-glucosidase enzyme for further investigation as anti-diabetic agents. (C) 2016 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2016.01.008

文献信息

• Rapid One-pot, Four Component Synthesis of Pyranopyrazoles Using Heteropolyacid Under Solvent-free Condition
  作者：Hemant V. Chavan、Santosh B. Babar、Rahul U. Hoval、Babasaheb P. Bandgar

  DOI：10.5012/bkcs.2011.32.11.3963

  日期：2011.11.20

  A series of pyranopyrazoles, was efficiently synthesized via one-pot, four component reaction of ethyl acetoacetate, hydrazine hydrate, aldehydes and malononitrile in the presence of catalytic amount silicotungstic acid under solvent free condition. NOE experiments confirmed that the product exist exclusively in the 2H form. The present protocol offers the advantages of clean reaction, short reaction time, high yield, easy purification and economic availability of the catalyst.

  一锅法制备了一系列吡喃吡唑啉衍生物，通过在没有溶剂条件下，以催化量的硅钨酸为催化剂，将乙酰乙酸乙酯、水合肼、醛和丙二腈进行四组分反应高效合成。NOE实验证实产物仅以2H形式存在。当前方法具有反应干净、反应时间短、产率高、易于纯化以及催化剂经济可得等优点。
• Synthesis of Substituted Pyranopyrazoles under Neat Conditions via a Multicomponent Reaction
  作者：Boreddy Reddy、Arasampattu Nagarajan

  DOI：10.1055/s-0029-1217526

  日期：2009.7

  A simple and efficient synthesis of pyranopyrazoles in good yields via a four-component reaction between an aromatic aldehyde, hydrazine hydrate, ethyl acetoacetate and malononitrile under neat conditions is described.

  描述了一种简单高效的吡喃并吡唑合成方法：在无溶剂条件下，通过芳香醛、水合肼、乙酰乙酸乙酯与丙二腈的四组分反应，以良好的产率得到目标产物。
• Fast synthesis of pyrano[2,3-c]pyrazoles: strong effect of Brönsted and Lewis acidic ionic liquids
  作者：Abdol R. Hajipour、Morteza Karimzadeh、Hamed Tavallaei

  DOI：10.1007/s13738-014-0561-0

  日期：2015.6

  approach, four-component synthesis of some pyrano[2,3-c]pyrazoles by [ChCl][ZnCl2]2 and [H-NMP]HSO4 as inexpensive and recyclable acidic ionic liquids were investigated. Excellent yields of products were obtained using both environmentally friendly safe ionic liquids. A comparative study of [ChCl][ZnCl2]2 as Lewis acidic ionic liquid and [H-NMP]HSO4 as Brönsted acidic ionic liquid was also carried out

  以一种独特的方法，研究了由[ChCl] [ZnCl 2 ] 2和[H-NMP] HSO 4作为廉价且可回收的酸性离子液体，对一些吡喃并[2,3- c ]吡唑进行四组分合成的方法。使用两种环境友好的安全离子液体均可获得优异的产品收率。还对作为路易斯酸性离子液体的[ChCl] [ZnCl 2 ] 2和作为布朗斯台德酸性离子液体的[H-NMP] HSO 4进行了比较研究。结果表明，与已报道的碱性离子液体相比，这些离子液体的优点是反应时间短，没有副产物和可重复使用。
• A new convenient four-component synthesis of 6-amino-2H, 4H-pyrano[2,3-c]pyrazole-5-carbonitriles and one-pot synthesis of 6 ′-amino-5-cyano-1,2-dihydrospiro-[(3H)-indole-3,4 ′-(4 ′H)-pyrano[2,3-c]pyrazol]-2-ones
  作者：Yu. M. Litvinov、L. A. Rodinovskaya、A. M. Shestopalov

  DOI：10.1007/s11172-009-0328-4

  日期：2009.11

  A new convenient method for the synthesis of 6-amino-2H,4H-pyrano[2,3-c]pyrazole-5-carbonitriles, namely, four-component condensation of carbonyl compounds (aromatic aldehydes, heterocyclic ketones), malononitrile, β-keto esters, and hydrazine hydrate in ethanol in the presence of triethylamine as a catalyst, which occurs selectively, is developed. One-pot two-step modification of this method is proposed

  一种合成6-氨基-2H,4H-吡喃并[2,3-c]吡唑-5-腈的便捷新方法，即羰基化合物（芳香醛、杂环酮）、丙二腈、β四组分缩合在三乙胺作为催化剂存在的情况下，在乙醇中的酮酯和水合肼被开发出来，这种反应是选择性发生的。该方法的一锅两步改进用于合成螺[(3 H)-吲哚-3,4'-(4'H)-吡喃并[2,3-c]吡唑]-2-酮.
• Alpha-Casein: an efficient, green, novel, and eco-friendly catalyst for one-pot multi-component synthesis of bis (pyrazol-5-ols), dihydro-pyrano[2,3-c]pyrazoles and spiropyranopyrazoles in an environmentally benign manner
  作者：Jalili Milani、Malek Taher Maghsoodlou、Nourallah Hazeri、Mahmoud Nassiri

  DOI：10.1007/s13738-019-01641-2

  日期：2019.8

  time, alpha-Casein was used as an efficient and eco-friendly catalyst for an effective and facile preparation of dihydropyranopyrazoles and spiropyranopyrazoles. The synthesis of bis (pyrazol-5-ols) derivatives was developed via one-pot, pseudo-five-component condensation, and the target dihydropyrano[2,3-c]pyrazoles and spiropyranopyrazoles were prepared by one-pot four-component reaction. This new

  首次将α-酪蛋白用作有效，简便地制备二氢吡喃并吡咯和螺吡喃并吡咯的有效和环保催化剂。通过一锅，拟五组分缩合反应开发了双（吡唑-5-醇）衍生物，并通过一锅四组分反应制备了目标二氢吡喃并[2,3- c ]吡唑和螺吡喃并吡唑。这种使用α-酪蛋白的新方法是一种绿色，可回收，无毒且可商购的催化剂，具有以下优点：条件温和，反应时间短，易于后处理，无需柱色谱法且收率高。使其比其他环境合成协议更经济的产品。