2-amino-4-(4-(dimethylamino)phenyl)-5-oxo-5,6,7,8-tetrahydro-5-4H-chromene-3-carbonitrile

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-amino-4-(4-(dimethylamino)phenyl)-5-oxo-5,6,7,8-tetrahydro-5-4H-chromene-3-carbonitrile
• 英文别名: 2-amino-4-(4-dimethylaminophenyl)-5-oxo-5,6,7,8-tetrahydro-4H-1-benzopyran-3-carbonitrile；2-amino-4-(4-(dimethylamino)phenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile；2-amino-4-(4-dimethylamino-phenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile；2-amino-4-(4-dimethylaminophenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile；2-amino-4-[4-(dimethylamino)phenyl]-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile；2-amino-4-[4-(dimethylamino)phenyl]-5-oxo-4,6,7,8-tetrahydrochromene-3-carbonitrile
• 化学式: C₁₈H₁₉N₃O₂
• 分子量: 309.368
• InChiKey: WSXGCUXQFDNNOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  79.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-amino-4-(4-(dimethylamino)phenyl)-5-oxo-5,6,7,8-tetrahydro-5-4H-chromene-3-carbonitrile 在 甲酸 作用下， 反应 70.0h， 以39%的产率得到4-(4-dimethylaminophenyl)-3,4,7,8-tetrahydroquinoline-2,5-(1H,6H)-dione
  参考文献：
  名称：

  Mishriky; Girgis; Asaad, Bollettino Chimico Farmaceutico, 2001, vol. 140, # 3, p. 129 - 139

  摘要：

  DOI：
• 作为产物：
  描述：

  ((4-(二甲基氨基)苯基)亚甲基)甲烷-1,1-二甲腈 、 1,3-环己二酮 在 吗啉 作用下， 以 甲醇 为溶剂， 反应 10.0h， 以80%的产率得到2-amino-4-(4-(dimethylamino)phenyl)-5-oxo-5,6,7,8-tetrahydro-5-4H-chromene-3-carbonitrile
  参考文献：
  名称：

  Mishriky; Girgis; Asaad, Bollettino Chimico Farmaceutico, 2001, vol. 140, # 3, p. 129 - 139

  摘要：

  DOI：

文献信息

• A cytochrome c-urea functionalized dipeptide conjugate: an efficient HBD framework to synthesize 4<i>H</i>-pyrans <i>via</i> one-pot multicomponent reaction
  作者：Sanjeev Saini、Mayank、Navneet Kaur、Narinder Singh

  DOI：10.1039/c9gc03512e

  日期：——

  This work is focused on the development of an efficient and green protocol for the one-pot multicomponent synthesis of a series of 4H-pyran derivatives.

  这项工作专注于开发一个高效且环保的一锅多组分合成协议，用于合成一系列4H-吡喃衍生物。
• Synthesis, molecular modeling and BACE-1 inhibitory study of tetrahydrobenzo[b] pyran derivatives
  作者：Vijaya Bhaskar、Reshma Chowdary、Sheshagiri R. Dixit、Shrinivas D. Joshi

  DOI：10.1016/j.bioorg.2018.11.023

  日期：2019.3

  documented as one of the possible therapeutic targets for the treatment of Alzheimer's disease. In this paper, we report the synthesis and the for β-secretase (BACE-1) inhibitory activity of new series of tetrahydrobenzo [b] pyran derivatives. One-pot synthesis of tetrahydrobenzo [b] pyrans was carried out by condensing aromatic aldehyde, malononitrile and 1,3-cyclohexanedione using ionic liquid 1-butyl-3-methyl

  β-分泌酶（BACE1）已被广泛证明是治疗阿尔茨海默氏病的可能治疗靶标之一。在本文中，我们报告了新系列的四氢苯并[b]吡喃衍生物的合成及其对β-分泌酶（BACE-1）的抑制活性。一锅法合成四氢苯并[b]吡喃是通过在水性醇介质中使用离子液体1-丁基-3-甲基咪唑鎓氯化物（[bmIm] Cl-）缩合芳族醛，丙二腈和1,3-环己二酮来进行的。乙醇和水的比例为1：2，可使所有反应物保持在溶液中，这有助于反应并非常容易地形成产物。对合成的化合物进行BACE1抑制分析，六个化合物4d，4e，4f，4h，4i和4p在微摩尔水平显示出显着的IC50值。在这六种活性化合物中，4e是一种潜在的抑制剂，其IC50值在纳摩尔范围内。所有合成的化合物都停靠在β-分泌酶的活性位点上。
• Cheap thiamine hydrochloride as efficient catalyst for synthesis of 4H-benzo[b]pyrans in aqueous ethanol
  作者：Lu Chen、Sunan Bao、Lixiang Yang、Xian Zhang、Bin Li、Yibiao Li

  DOI：10.1007/s11164-016-2843-x

  日期：2017.7

  Preparation of pharmaceutically active 2-amino-4H-pyran derivatives has been achieved using cheap thiamine hydrochloride as catalyst. A wide range of aromatic aldehydes easily undergo condensation with malononitrile and several kinds of 1,3-cyclohexanedione under mild condition to afford the desired product with good purity in excellent yield. This protocol has various advantages as a simple, clean, and environmentally benign three-component process.

  利用廉价原料盐酸硫胺素作为催化剂，已经实现了具有药理活性的2-氨基-4H-吡喃衍生物的制备。多种芳香醛可以在温和条件下与丙二腈以及几种1,3-环己二酮发生缩合反应，得到纯度高且产率优异的目标产物。该方法作为一个简便、清洁且环境友好的三组分反应，具有多种优势。
• Practical and Green Protocol for the Synthesis of Substituted 4<i>H</i>-Chromenes Using Room Temperature Ionic Liquid Choline Chloride-Urea
  作者：C. N. Revanna、T. R. Swaroop、G. M. Raghavendra、D. G. Bhadregowda、K. Mantelingu、K. S. Rangappa

  DOI：10.1002/jhet.880

  日期：2012.7

  An efficient and convenient synthesis of substituted 4H‐chromenes is described using room temperature ionic liquid (RTIL) choline chloride–urea in one pot under solvent free conditions. Three‐component Knoevenagel condensation of an aromatic aldehyde, with an active methylene compound, and a cyclohexane dione is reported. This new approach has advantage of excellent yields (82–96%), clean reaction

  在无溶剂条件下，使用室温离子液体（RTIL）氯化胆碱-尿素在一个锅中描述了一种高效便捷的取代4 H-色烯的合成方法。据报道，芳香醛与活性亚甲基化合物和环己烷二酮的三组分Knoevenagel缩合反应。这种新方法的优点是在室温下具有优异的收率（82–96％），干净的反应和较短的反应时间（15–30分钟）。
• A Facile, Eco-friendly, Proton Donor-Acceptor Catalyzed, One-Pot, Three-Component Synthesis of Tetrahydrobenzo[b]pyrans
  作者：A. Indrasena、Sd. Riyaz、A. Naidu、P.K. Dubey

  DOI：10.14233/ajchem.2014.15657

  日期：——

  Piperidinium acetate catalyzed, three-component cyclocondensation between aryl aldehydes (1), malononitrile (2) and cyclic-1,3-diketo compounds (3) in the eco-friendly and universal solvent water at room temperature for 0.5 h, resulted in the formation of tetrahydro[b]pyran derivatives (4). The formation of 4 could also be established in a step-wise fashion by isolating independently each of the intermediates benzylidine malononitrile 5 and benzylidine cyclohexane-1,3-dione 6 and treating them subsequently with 3 and 2, respectively to obtain benzopyrans 4. Mechanistic studies on the formation of 4 from 1, 2 and 3 are reported. Further, the synthesis of 4 could also be achieved in two variable but identical end-product giving tandem syntheses by treating 1 with 2 and then with 3 giving 4 or by treating 1 with 3 and then with 2 giving 4. All the products were suitably characterized using NMR, IR and Mass spectroscopy.

  在环境友好且通用的溶剂水中，以室温进行0.5小时，采用哌啶铵乙酸盐催化，苯基醛（1）、氟代酸（2）和环状1,3-二酮化合物（3）之间的三组分环缩合反应，形成四氢[b]吡喃衍生物（4）。4的形成也可以通过逐步法来实现，分别独立分离每个中间体苄亚基氟代酸（5）和苄亚基环己烷-1,3-二酮（6），然后分别与3和2处理以获得苯并吡喃（4）。报告了关于从1、2和3形成4的机理研究。此外，通过将1与2反应后再与3处理或将1与3反应后再与2处理，都可以获得4，从而实现两种可变但相同的最终产物的串联合成。所有产品均通过NMR、IR和质谱进行了适当表征。