N-functionalization of uracil derivatives:: synthesis of chiral 2-(3-methyl-5-nitro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)alkanoic acids and their methyl esters

3-Methyl-5-nitro-1-(4-nitrophenyl)uracil has been obtained by regioselective arylation of uracil using 4-nitrofluorobenzene, followed by methylation at the nitrogen atom N-3 and subsequent nitration of the uracil ring. 3-Methyl-5-nitro-1-(4-nitrophenyl)uracil, which was treated with either certain amino acids methyl ester or free amino acids underwent an ANRORC type substitution reaction. Appropriate methyl 2-substituted alkanoates or alkanoic acids containing 3-methyl-5-nitrouracil parts were obtained in satisfactory yields. A similar reaction can be carried out using 5-cyano-3-methyl-1-(4-nitrophenyl)uracil as a substrate. (c) 2005 Elsevier Ltd. All rights reserved.