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Facile Synthesis and Anticancer Activity of Novel 4-Aminothieno[2,3-d]pyrimidines and Triazolothienopyrimidines
Organic Preparations and Procedures International ( IF 1.2 ) Pub Date : 2019-10-16 , DOI: 10.1080/00304948.2019.1666635
Fatma S. M. Abu El-Azm 1 , Amira T. Ali 1 , Mohamed H. Hekal 1
Affiliation  

Thienopyrimidines play important roles in numerous biological activities. They are known to display multiple therapeutic properties, such as anti-inflammatory, antimicrobial, antiproliferative, antidiabetic and analgesic activities. They are structural analogs of biogenic purines and can be considered as potential nucleic acid antimetabolites. Consequently, preparation of thienopyrimidine derivatives with interesting biological activities has attracted particular attention and a variety of methods for the synthesis of thienopyrimidines have been developed. The most common method for synthesis of 4-aminothieno[2,3-d]pyrimidines involves the thermal ring closure of 2-(benzoylthioureido)thiophene-3-carbonitriles effected by sodium hydroxide in an ethanol–water mixture, followed by the addition of alkyl halides. In continuation of our interest in synthesizing biologically active heterocyclic compounds, we therefore designed a simple and facile synthesis of key reactant 2. Tetrahydrobenzo[b]thiophene derivative A was reacted with chloroacetyl chloride, furnishing the corresponding N-chloroacetylamino derivative 1 by a modified procedure of Sauter et al. (Scheme 1). Compound 1 was treated with ammonium thiocyanate in refluxing ethanol, affording the compound 2 rather than the 2-imino-4-oxothiazolidine derivative 3 (Scheme 1). In the infrared spectrum of the product, the appearance of strong absorption bands for the NH2 group at 3296 and 3134 cm 1 and the carbonyl ester group at 1735 cm 1 along with the absence of any absorption band for the nitrile group is in agreement with the structure 2 and ruled out the 2-imino-4-oxothiazolidine derivative 3. Moreover, in the H-NMR spectrum of compound 2, the appearance of a broad signal attributable to the NH2 protons at d 6.8 ppm and a quartet at d 4.12 ppm and a triplet at d 1.19 ppm confirmed the outcome of the cyclization reaction. Hydrazinolysis of compound 2 using hydrazine hydrate (1:1) in refluxing ethanol afforded colorless crystals which were identified as acetohydrazide 4 (Scheme 2). A number of novel 4-aminothieno[2,3-d]pyrimidines were then synthesized using the acid hydrazide 4 and treatment with different C-electrophiles. Thus, refluxing compound 4

中文翻译:

新型4-氨基噻吩并[2,3-d]嘧啶和三唑噻吩并嘧啶的简便合成及其抗癌活性

噻吩并嘧啶在许多生物活动中起着重要作用。众所周知,它们具有多种治疗特性,例如抗炎、抗菌、抗增殖、抗糖尿病和镇痛活性。它们是生物嘌呤的结构类似物,可被视为潜在的核酸抗代谢物。因此,具有令人感兴趣的生物活性的噻吩并嘧啶衍生物的制备引起了特别关注,并且已经开发了多种用于合成噻吩并嘧啶的方法。合成 4-氨基噻吩并[2,3-d]嘧啶的最常用方法包括在乙醇-水混合物中通过氢氧化钠对 2-(苯甲酰硫脲基)噻吩-3-腈进行热闭环,然后加入卤代烷。为了继续我们对合成生物活性杂环化合物的兴趣,我们设计了一种简单易行的关键反应物 2 合成方法。 四氢苯并 [b] 噻吩衍生物 A 与氯乙酰氯反应,通过改进的程序提供相应的 N-氯乙酰氨基衍生物 1 Sauter 等人。(方案1)。在回流的乙醇中用硫氰酸铵处理化合物 1,得到化合物 2 而不是 2-亚氨基-4-氧噻唑烷衍生物 3(方案 1)。在产品的红外光谱中,NH2 基团在 3296 和 3134 cm 1 处和羰基酯基团在 1735 cm 1 处出现强吸收带,而腈基没有任何吸收带,这与结构 2 并排除了 2-imino-4-oxothiazolidine 衍生物 3。此外,在化合物 2 的 H-NMR 谱中,出现的宽信号归因于 d 6.8 ppm 处的 NH2 质子和 d 4.12 ppm 处的四重峰和 d 1.19 ppm 处的三重峰,证实了环化反应的结果。在回流乙醇中使用水合肼 (1:1) 对化合物 2 进行肼解,得到无色晶体,经鉴定为乙酰肼 4(方案 2)。然后使用酰肼 4 并用不同的 C-亲电试剂处理合成了许多新型 4-氨基噻吩并 [2,3-d] 嘧啶。因此,回流化合物 4 1) 在回流的乙醇中得到无色晶体,鉴定为乙酰肼 4(方案 2)。然后使用酰肼 4 并用不同的 C-亲电试剂处理合成了许多新型 4-氨基噻吩并 [2,3-d] 嘧啶。因此,回流化合物 4 1) 在回流的乙醇中得到无色晶体,鉴定为乙酰肼 4(方案 2)。然后使用酰肼 4 并用不同的 C-亲电试剂处理合成了许多新型 4-氨基噻吩并 [2,3-d] 嘧啶。因此,回流化合物 4
更新日期:2019-10-16
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