Synthesis of 5, 6-disubstitued pyrimidines of biological improtance

Abstract

In view of the significant biological activities of various 5 and 6- substituted uracils and. related pyrimidine derivatives, a facile method for the synthesis of a number of 5, 6- disubstituted pyrimidines was developed (Scheme-I). 2, 4-Dichloro pyrimidine -6- carbonyl chloride 2 was synthesized by refluxing orotic acid 1 with phosphorus oxychloride and phosphorus pentachloride. Compound 2 underwent a smooth Friedel- Crafts reaction with a number of substituted benzene derivatives. 2, 4 Dichloro-6-pbromobenzoyl pyrimidine 3 and 2, 4- dichloro-6-p-methoxy benzoyl pyrimidine 4 were converted to the corresponding dimethoxy pyrimidine;6 & 7 on treatment with sodium methoxide in me,thanol. 2, 4- Dicholoropyrimidine -6-carbonyl chloride was also converted to 2, 4- dimethyl -6-methyl orotate 8 by refl.uxing with sodium methoxide in methanol for 6 hr. The iodination reaction was attempted by several methods but only NIS-TFA-TFAA method gave the desired products. 2, 4-Dimethyl -5-iodo-6-p' bromobenzoyl pyrimidine 9 and 2, 4-dimethoxy-5ciodo-6-methyl orotate 11 were subjected to palladium-catalyzed reaction to yield 5:alkynyl substituted product and cyclized product. The structure of the synthesized products were established from their analytical and spectroscopic data..........................................................