Synthesis of dimethoxypyrimidines and uracils with novel C-5 substituents

Abstract

5-Iodo-2,4-dimethoxypyrimidine 1 on treatment with copper(I) 3-tetrahydropyran-2-yloxyprop-1-ynide was converted into 2,4-dimethoxy-5-(3-tetrahydropyran-2-yloxyprop-1-ynyl)pyrimidine 2 which on treatment with toluene-p-sulphonic acid in methanol led to 5-(3-hydroxyprop-1-ynyl)2,4-dimethoxypyrimidine 3. This was oxidised with Swern reagent to 5-(formylethynyl)-2,4-dimethoxypyrimidine 4. Compound 4 on treatment with a number of Grignard reagents gave 5-[(3-alkyl or aryl-3-hydroxy)prop-1-ynyl]-2,4-dimethoxypyrimidines 6–12. These were oxidised to 5-(acylethynyl)-2,4-dimethoxypyrimidines 13–19. On treatment with 6 mol dm^–3 hydrochloric acid, 5-(acylethynyl)-2,4-dimethoxypyrimidines were converted into 5-(2-acyl-l-chlorovinyl)uracils 20–23. Compounds 20–22 were dehydrohalogenated with sodium hydroxide in 95% ethanol to 5-(acylethynyl)uracils 24–26.