SYNTHESIS OF LABELED 5-HYDROXY-6-METHYL(4,6-C-14)URACIL

Beta-uramino(1,3-C-14)crotonic ester is prepared for the first time by condensation of urea with labeled (2,4-C-14)acetoacetic ester in the presence of ethanol and concentrated HCl. Treatment of beta-uramino(1, 3-C-14)crotonic ester with base gives the Na salt of beta-uramino(1,3- C-14)crotonic acid. Hydrolysis of the above acid by HCl at 65-degrees- C gives 6-methyl(4,6-C-14)uracil. The oxidation of 6-methyl(4,6-C-14)u racil by solid ammonium persulfate in basic solution at 40-70-degrees- C gives the intermediate 6-methyl(4,6-C-14)uracil-5-ammonium sulfate i n 35% yield with 99-100% purity. Hydrolysis of pure 6-methyl(4,6-C-14) uracil-5-ammonium sulfate by H2SO4 at 85-95-degrees-C gives 5-hydroxy- 6-methyl(4,6-C-14)uracil in 95-100% yield with 99-100% purity. The pro duct purity is proved by TLC, melting point, elemental analysis, and I R, UV, and PMR spectra.