Abstract

A simple, efficient, cost-effective and environmentally friendly synthesis of new isoxazolyl pyrido[2,3-d]pyrimidine derivatives 11 has been developed from 4-amino-3-methyl-5-styrylisoxazoles 7 by using polyethylene glycol-400 (PEG-400) as a solvent as well as catalyst. Compound 7 on treatment with methyl-2-chloronicotinate 8 in the presence of PEG-400 to obtain the corresponding (E)-methyl-2-((3-methyl-5-styrylisoxazol-4-yl)amino)nicotinates 9, which was further treated with different arylisothiocyanates 10 in the presence of PEG-400 under heating condition afforded the target products isoxazolyl pyrido[2,3-d]pyrimidines 11 in good to excellent yields. The target compounds 11a-y was also evaluated for their antimicrobial and anti-inflammatory activities. Among the tested compounds, the compounds 11w, 11x, and 11y showed significant antimicrobial activity and potent anti-inflammatory activity as that of standard drugs. The superiority of this method is catalyst free, operational simplicity, environmental safety; metal free, broad substrate scope, easy purification, high yields and PEG-400 can be recovered and reused.

摘要

一种新的异恶唑基吡啶并[2,3- d ]嘧啶衍生物11的简单，有效，经济高效且环境友好的合成方法是使用聚乙二醇400（PEG）从4-氨基-3-甲基-5-苯乙烯基恶唑7合成的。 -400）作为溶剂和催化剂。在PEG-400存在下，用-2-氯烟酸甲酯8处理化合物7，以获得相应的（E）-甲基-2-（（3-甲基-5-苯乙烯基恶唑-4-基）氨基）烟酸酯9，在加热条件下，在PEG-400存在下，用不同的芳基异硫氰酸酯10进一步处理，得到目标产物异恶唑基吡啶基[2,3- d]嘧啶11的收率高至优异。还评估了目标化合物11a-y的抗微生物和抗炎活性。在测试化合物中，化合物11w，11x和11y与标准药物相比具有显着的抗菌活性和有效的抗炎活性。该方法的优点是无催化剂，操作简便，环境安全。不含金属，底物范围广，易于纯化，高收率，并且可以回收和再利用PEG-400。