Synthesis of the derivatives of 6-amino-uracil labelled with C.

The radioactively labelled 6-amino-5-nitroso-uracil (1) and 5-acetyl-6-amino-1,3-dimethyl-uracil (2) were required for metabolic studies to assess their suitability as drug candidates. A common precursor for both compounds was [cyano- C]cyanoacetic acid (6), readily prepared from potassium [ C]cyanide. ACS reagents, namely, diethyl ether, acetic acid and acetic anhydride, had to be rigorously repurified to achieve a successful synthesis of C-labelled compounds on a tenth-of-a-milligramme scale. 6-Amino-5-nitroso-[6- C]uracil (1- C) (0.55 mCi) was prepared with radiochemical purity > 98% and specific activity (SA) = 55.6 mCi/mmol. 5-Acetyl-6-amino-1,3-dimethyl-[6- C]uracil (2- C) (8 mCi) was prepared with radiochemical purity > 97% and SA = 55.6 mCi/mmol. It has been shown that a SA assay can be made from standard C NMR spectra, thus avoiding the need to perform lengthier inverse-gated C NMR experiments.