2-amino-4-(4-dimethylaminophenyl)-7-hydroxy-4H-chromene-3-carbonitrile | 160111-61-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 新黄酮类化合物
• 英文名称: 2-amino-4-(4-dimethylaminophenyl)-7-hydroxy-4H-chromene-3-carbonitrile
• 英文别名: 2-amino-4-[4-(dimethylamino)phenyl]-7-hydroxy-4H-chromene-3-carbonitrile
• CAS: 160111-61-5
• 化学式: C₁₈H₁₇N₃O₂
• 分子量: 307.352
• InChiKey: JXZIXFRUSHDGMU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  82.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-amino-4-(4-dimethylaminophenyl)-7-hydroxy-4H-chromene-3-carbonitrile 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.67h， 生成
  参考文献：
  名称：

  新型1 H -1,2,3-三唑系4 H-色烯基-d-葡萄糖偶联物的高效点击化学：体外抗菌，MRSA和抗真菌活性的设计，合成和评估

  摘要：

  该系列的2-氨基-7-炔丙氧基-4- ħ色烯-3-腈5A-T是从相应的2-氨基-7- phydroxy-4中合成ħ色烯-3-腈图4a-T和炔丙基溴。在这些合成中使用了两种方法：K 2 CO 3 /丙酮和NaH / DMF方法，产率分别为65-89％和80-96％。1个ħ -1,2,3-三唑系留4H-苯并吡喃d葡萄糖偶联物7A-T使用炔丙基的点击化学醚合成5A-T和四- ö乙酰基β- d-吡喃葡萄糖基叠氮化物。[电子邮件保护]是该化学反应的最佳催化剂。1 H -1,2,3-三唑的产率为80–97.8％。在体外评估所有三唑7a-t的抗微生物活性。在MIC值为1.56-6.25μM的测试化合物中，有四种化合物对抗枯草芽孢杆菌，四种化合物对抗金黄色葡萄球菌，四种化合物对抗表皮葡萄球菌；有5种抗大肠杆菌的化合物，4种抗肺炎克雷伯菌的化合物，5种抗铜绿假单胞菌的化合物，和6种抗鼠伤寒沙门氏菌的化合物。

  DOI：

  10.1016/j.ejmech.2019.01.060
• 作为产物：
  描述：

  对二甲氨基苯甲醛 以 乙醇 为溶剂， 反应 28.0h， 生成 2-amino-4-(4-dimethylaminophenyl)-7-hydroxy-4H-chromene-3-carbonitrile
  参考文献：
  名称：

  Synthesis, Structure–Activity Relationships and Brain Uptake of a Novel Series of Benzopyran Inhibitors of Insulin-Regulated Aminopeptidase

  摘要：

  Peptide inhibitors of insulin-regulated aminopeptidase (IRAP) enhance fear avoidance and spatial memory and accelerate spatial learning in a number of memory paradigms. Using a virtual screening approach, a series of benzopyran compounds was identified that inhibited the catalytic activity of IRAP, ultimately resulting in the identification of potent and specific inhibitors. The present study describes the medicinal chemistry campaign that led to the development of the lead candidate, 3, highlighting the key structural features considered as critical for binding. Furthermore, the in vivo pharmacokinetics and brain uptake of compounds (1 and 3) were assessed in rats and were complemented with in vitro human and rat microsomal stability studies. Following intravenous administration to rodents, 3 exhibits brain exposure, albeit it is rapidly converted to 1, a compound which also exhibits potent inhibition of IRAP.

  DOI：

  10.1021/jm401540f

文献信息

• An expeditious synthesis of novel pyranopyridine derivatives involving chromenes under controlled microwave irradiation
  作者：Dushyant Singh Raghuvanshi、Krishna Nand Singh

  DOI：10.3998/ark.5550190.0011.a25

  日期：——

  An efficient synthesis of novel pyrano[2,3-b]pyridine derivatives has been achieved by the cyclocondensation of 2-amino-3-cyano-4H-chromenes and cyclohexanone in the presence of aluminium chloride under controlled microwave irradiation. The experimental conditions have been thoroughly optimized and established, allowing significant rate enhancements and excellent yields. The starting 4H-chromenes were

  2-氨基-3-氰基-4H-色烯和环己酮在氯化铝存在下，在受控的微波辐射下进行环缩合反应，实现了新型吡喃并[2,3-b]吡啶衍生物的有效合成。实验条件已经过彻底优化和建立，可以显着提高速率和优异的产量。使用一锅 DBU 催化的微波诱导间苯二酚、丙二腈和芳香醛的多组分缩合获得起始 4H-色烯。
• A facile and efficient synthesis of 2-amino-3-cyano-4H-chromenes and tetrahydrobenzo[b]pyrans using 2,2,2-trifluoroethanol as a metal-free and reusable medium
  作者：Samad Khaksar、Ahmad Rouhollahpour、Saeed Mohammadzadeh Talesh

  DOI：10.1016/j.jfluchem.2012.05.014

  日期：2012.9

  A highly efficient one-pot three-component regioselective synthesis of 2-amino-3-cyano-4H-chromene and tetrahydrobenzo[b]pyran derivatives has been developed by annulation of aldehydes, malononitrile, and resorcinol or dimedone under reflux conditions in 2,2,2-trifluoroethanol without the use of a catalyst or any other additive.

  通过在回流条件下2醛，丙二腈和间苯二酚或二甲酮的环化反应，已经开发出了一种高效的一锅三组分区域选择性合成2-氨基-3-氰基-4 H-色烯和四氢苯并[ b ]吡喃衍生物的方法。 ，2,2-三氟乙醇，不使用催化剂或任何其他添加剂。
• Saccharose as a new, natural, and highly efficient catalyst for the one-pot synthesis of 4,5-dihydropyrano[3,2-c]chromenes, 2-amino-3-cyano-4H-chromenes, 1,8-dioxodecahydroacridine, and 2-substituted benzimidazole derivatives
  作者：Malek Taher Maghsoodlou、Nourallah Hazeri、Mojtaba Lashkari、Fereshteh Nejad Shahrokhabadi、Behzad Naghshbandi、Mohammad Saeed Kazemi-doost、Mahnaz Rashidi、Fatemeh Mir、Mehrnoosh Kangani、Sajjad Salahi

  DOI：10.1007/s11164-014-1793-4

  日期：2015.10

  Saccharose was applied as a green and natural catalyst for the one-pot, three-component condensation between aromatic aldehydes, malononitrile, and resorcinol, or 4-hydroxycoumarine to afford the corresponding pyran-annulated heterocyclic systems. This green methodology offers several advantages such as the use of a non-hazardous catalyst, easy access, clean work-up, excellent yields, short reaction time, and environmentally mild conditions. In addition, 1,8-dioxodecahydroacridine and 2-substituted benzimidazole derivatives have been synthesized from commercially available starting materials, arylaldehydes, dimedone, amines, or ammonium acetate and o-phenylenediamine using the mentioned catalyst.

  蔗糖被用作绿色和天然催化剂，进行芳香醛、马来腈和儿茶酚或4-羟基香豆素之间的一锅三组分缩合反应，生成相应的吡喃缩合杂环体系。这种绿色方法具有多个优点，如使用无害催化剂、易于获得、清洁的后处理、优良的产率、短的反应时间以及环保的温和条件。此外，1,8-二氧代十氢吡啶和2-取代苯并咪唑衍生物是通过上述催化剂从商业可获得的起始材料（芳香醛、二酮、胺或醋酸铵和邻苯二胺）合成的。
• Efficient tandem synthesis of a variety of pyran-annulated heterocycles, 3,4-disubstituted isoxazol-5(4H)-ones, and α,β-unsaturated nitriles catalyzed by potassium hydrogen phthalate in water
  作者：Hamzeh Kiyani、Fatemeh Ghorbani

  DOI：10.1007/s11164-014-1863-7

  日期：2015.10

  A variety of 4H-chromenes, benzochromenes, 4,5-dihydropyrano[3,2-c]chromenes, 4H-pyran-3-carboxylates, and 3,4-disubstituted isoxazol-5(4H)-ones have been synthesized in high yields by using potassium hydrogen phthalate (KHP) as an inexpensive, commercially available catalyst. It was found that the three-component tandem reaction enabled synthesis of pyran-annulated heterocycles in water at 50 °C. 3,4-Disubstituted isoxazol-5(4H)-ones were synthesized by use of 10 mol% KHP in water at room temperature. Also, treatment of methylene-containing compounds (malononitrile or ethyl cyanoacetate) with aromatic aldehydes in the presence of 5 mol% KHP resulted in α,β-unsaturated nitriles. The procedure is an easily performed, straightforward method for synthesis of a variety of pyran-annulated compounds, isoxazol-5(4H)-one-containing heterocycles, and Knoevenagel adducts. The reaction is safe, uses mild conditions, and is environmentally benign. Other notable advantages are reuse of the catalyst, no use of hazardous organic solvents, and ease of work-up.

  合成了一系列4H-克罗梅、苯并克罗梅、4,5-二氢吡喃[3,2-c]克罗梅、4H-吡喃-3-羧酸盐以及3,4-二取代的异噁唑-5(4H)-酮，采用了氢钾邻苯二甲酸盐（KHP）作为廉价的商业可得催化剂，得到了高产率。研究发现，这种三组分串联反应使得在50°C的水相中合成了吡喃环接合的杂环化合物。3,4-二取代的异噁唑-5(4H)-酮是在室温下使用10 mol% KHP水相合成的。此外，在存在5 mol% KHP的情况下，采用含亚甲基的化合物（如马来腈或乙基氰乙酸酯）与芳香醛的反应，得到了α,β-不饱和腈。该方法是一种简单易行的合成多种吡喃环接合化合物、含异噁唑-5(4H)-酮的杂环化合物和Knoevenagel加成物的直截了当的方法。该反应安全、条件温和且环境友好。其他显著优点包括催化剂的重复使用、不使用有害有机溶剂以及简便的后处理。
• Highly efficient organocatalytic synthesis of diverse and densely functionalized 2-amino-3-cyano-4H-pyrans under mechanochemical ball milling
  作者：Mohammad G. Dekamin、Mohammad Eslami

  DOI：10.1039/c4gc00411f

  日期：——

  one-pot three-component and environmentally benign approach for the synthesis of a wide range of densely functionalized 2-amino-3-cyano-4H-pyran annulated derivatives has been described by the reaction of aryl aldehydes, malononitrile and diverse electron-rich phenolic or enolizable carbonyl compounds under mechanochemical ball milling conditions in the presence of potassium phthalimide (POPI), as a mild

  通过芳基醛，丙二腈和各种电子的反应，已经描述了一种改进的一锅三组分且对环境无害的方法，可用于合成各种稠密的官能化的2-氨基-3-氰基-4 H-吡喃环化的衍生物。在机械化学球磨条件下，在环境温度下，在邻苯二甲酰亚胺钾（POPI）（作为温和的碱性有机催化剂）的存在下，制备富含酚的或可烯化的羰基化合物。与传统方法相比，此绿色方案的显着优势是定量产量高，避免使用任何无危险的无过渡金属的催化剂或溶剂，在环境温度下反应时间更短，成本较低且后处理程序简单。