4-propylaminocoumarin-6-carbaldehyde | 136806-22-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 4-propylaminocoumarin-6-carbaldehyde
• 英文别名: 4-Propylamino-3-cumarincarbaldehyd；2H-1-Benzopyran-3-carboxaldehyde, 2-oxo-4-(propylamino)-；2-oxo-4-(propylamino)chromene-3-carbaldehyde
• CAS: 136806-22-9
• 化学式: C₁₃H₁₃NO₃
• 分子量: 231.251
• InChiKey: HKFAIEFECPBETD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-propylaminocoumarin-6-carbaldehyde 、 丁炔二酸二甲酯 在 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 以77 %的产率得到dimethyl 5-oxo-1-propyl-1,2-dihydro-5H-chromeno[4,3-b]pyridine-2,3-dicarboxylate
  参考文献：
  名称：

  用于治疗阿尔茨海默病的双功能胆碱酯酶和碳酸酐酶抑制剂：香豆素-二氢吡啶衍生物的设计、合成、体外和计算机评价

  摘要：

  阿尔茨海默氏病 (AD) 是一种复杂、进行性和主要形式的认知障碍。胆碱酯酶 (ChE) 抑制剂在治疗 AD 中的有用作用已得到充分证明。除 ChE 抑制剂外，多项研究证实，抑制人碳酸酐酶 (hCAs) 有助于 AD 治疗。为了引入有效的 ChE 和 hCA 抑制剂，基于有效药效团的分子杂交设计了新的香豆素-二氢吡啶衍生物 ( 6a-m) 。由三步组成的简单合成路线用于合成标题化合物6a-m. 后一种化合物针对乙酰胆碱酯酶 (AChE)、丁酰胆碱酯酶 (BChE) 和两种重要的 hCA 亚型（包括 hCA I 和 hCA II）进行了评估。体外试验的结果表明，化合物6b、6f和6i是最有前途的抗 AChE 和 BChE 衍生物，而抗研究的 hCA 最有效的化合物是化合物6g、6i和6j。此外，使用 Autodock 软件和 preADMET 在线软件对最有效的化合物进行计算机筛选，以分别识别结合模式和预测药代动力学特性。

  DOI：

  10.1016/j.molstruc.2022.134767
• 作为产物：
  描述：

  4-氯-3-甲酰基香豆素 以 甲醇 为溶剂， 反应 2.0h， 生成 4-propylaminocoumarin-6-carbaldehyde
  参考文献：
  名称：

  Phosphorylation and Amine-induced Dephosphorylation of 4-Chlorocoumarin-3-carboxaldehyde and 4-Chloro-3-(β,β-dicyanoethenylidene)coumarin

  摘要：

  4-Chlorocoumarin-3-carboxaldehyde (1) and 4-chloro-3-(beta,beta-dicyanoethenylidene)coumarin (2) produce their respective 1:1 phosphonate adducts (5a-c) and (6a-c) upon reaction with the appropriate dialkylphosphonates (3a-c). Compounds 5 undergo dechlorination and dephosphorylation upon reaction with certain primary aliphatic amines to yield 9 (or 10) according to the nature of the amine used. Compounds 1 and 2 undergo dechlorination through reaction with hexamethyl-phosphorustriamide 4 to give the respective 4-dimethylamino-derivatives (11a and 11b). Structural reasonings for the new compounds are based on compatible analytical and spectroscopic measurements. The mechanism for formation of compounds 11 also is discussed.

  DOI：

  10.1080/713744562

文献信息

• Two Methods for the Preparation of 3-Dialkylaminomethyl Derivatives (Mannich Bases) of 4-Aminocoumarin: A New Type of Intramolecular Hydride Transfer
  作者：Ivo C. Ivanov、Stoyan K. Karagiosov

  DOI：10.1055/s-1995-3971

  日期：1995.6

  The transformation of 4-alkylaminocoumarin-3-carbaldehydes (1b-f) by treatment with secondary amines 2a-i into 3-dialkylaminomethyl-4-aminocoumarins 4a-i via intramolecular hydride transfer is reported. The structure of 4 was ascertained by independent Mannich reaction of 4-aminocoumarin (5) yielding the 3-dialkylaminomethyl derivatives 4a-e. By treatment of 1e with primary amine 6 only the usual Schiff base 7 was obtained.

  报道了通过与二级胺 2a-i 处理 4-烷基氨基香豆醛 (1b-f)，实现通过分子内氢转移转化为 3-二烷基氨基甲基-4-氨基香豆素 4a-i 的过程。 4 的结构通过独立的 Mannich 反应确认，该反应使用 4-氨基香豆素 (5) 生成 3-二烷基氨基甲基衍生物 4a-e。用初级胺 6 处理 1e，仅得到常规的舒夫碱 7。
• Synthesis of 2<i>H</i>-chromeno[4,3-<i>b</i>]pyridine-2,5(1<i>H</i>)-diones and related heterocycles<i>via</i>the erlenmeyer-ploechl reaction
  作者：Ivo Christov Ivanov、Toma Nikolaev Glasnov、Dieter Heber

  DOI：10.1002/jhet.5570420517

  日期：2005.7

  no[4,3-b]pyridine-2,5-diones 4a-j were synthesized from 4-alkylamino-coumarin-3-carbaldehydes 1 and 5(4H)-oxazolinones (azalactones) derived from N-acetylglycine (2a) and hippuric acid (2b). The intermediates 3 (3j isolated only) underwent spontaneous recyclization via opening of the azalactone and successive formation of the fused 2-pyridones 4. Attempts to synthesize the selected 2H-chromeno[3,4-f]-1

  由4-烷基氨基香豆素-3-甲醛1和5（4 H）-合成1,2-二氢-5 H- [1]苯并吡喃并[4,3 - b ]吡啶-2,5-二酮4a-j。由N-乙酰基甘氨酸（2a）和马尿酸（2b）衍生而来的恶唑啉酮（azalactones ）。中间体3（仅3j被分离）通过打开内酯基内酯和连续形成稠合的2-吡啶酮4进行自发的再循环。尝试合成所选的2 H -chromeno [3,4- f ] -1,7-萘啶6通过Vilsmeier的4e反应失败。相反，发生N-脱乙酰化，然后将氨基甲酰化为甲am7a。另外，通过使3-甲酰基-2-吡啶酮8与衍生自2a的乙二酸内酯和乙酸酐缩合获得吡喃并吡啶9a。
• Steinfuehrer, Thorsten; Hantschmann, Achim; Pietsch, Michael, Liebigs Annalen der Chemie, 1992, # 1, p. 23 - 28
  作者：Steinfuehrer, Thorsten、Hantschmann, Achim、Pietsch, Michael、Weissenfels, Manfred

  DOI：——

  日期：——
• A Convenient Approach to the Synthesis of Dialkyl 5‐Oxo‐1,2‐dihydro‐5<i>H</i>‐chromeno [4,3‐<i>b</i>]pyridine‐2,3‐dicarboxylates
  作者：Toma N. Glasnov、Ivo C. Ivanov

  DOI：10.1080/00397910801929465

  日期：2008.4.1

  Coumarin and its analogs are considered privileged scaffolds in the current synthetic and pharmacological research. The chemical behavior of enaminocarbaldehydes of the coumarin moiety under intramolecular Wittig reaction conditions in the presence of triphenylphosphine and dimethyl or diethyl acetylenedicarboxylates has been studied, resulting in the isolation of a series of dimethyl and diethyl 5-oxo-1,2-dihydro-5H-chromeno[4,3-b]pyridine-2,3-dicarboxylates in good to high yields.
• Phosphorylation and Amine-induced Dephosphorylation of 4-Chlorocoumarin-3-carboxaldehyde and 4-Chloro-3-(β,β-dicyanoethenylidene)coumarin
  作者：Maha Darwish Khidre

  DOI：10.1080/713744562

  日期：2003.10.1

  4-Chlorocoumarin-3-carboxaldehyde (1) and 4-chloro-3-(beta,beta-dicyanoethenylidene)coumarin (2) produce their respective 1:1 phosphonate adducts (5a-c) and (6a-c) upon reaction with the appropriate dialkylphosphonates (3a-c). Compounds 5 undergo dechlorination and dephosphorylation upon reaction with certain primary aliphatic amines to yield 9 (or 10) according to the nature of the amine used. Compounds 1 and 2 undergo dechlorination through reaction with hexamethyl-phosphorustriamide 4 to give the respective 4-dimethylamino-derivatives (11a and 11b). Structural reasonings for the new compounds are based on compatible analytical and spectroscopic measurements. The mechanism for formation of compounds 11 also is discussed.