Synthesis of tritium-labeled 5-fluorouracil and 5-fluorocytosine

Abstract

The effect of various catalysts and temperature on the solid-phase isotope exchange of 5-fluorouracil and 5-fluorocytosine with tritium was studied. The isotope exchange yielding the desired compounds is accompanied by dehalogenation and hydrogenation of the 5,6-double bond of the pyrimidine ring. Performing the reaction at a temperature below 160°C allowed the process to be carried out selectively, i.e., with the preservation of the functional groups and double bond in the starting compound. The yields of various products formed in the reactions of tritium with the above compounds were estimated. Synthesis conditions were found, and tritium-labeled 5-fluorouracil and 5-fluorocytosine were prepared with the molar radioactivity of 0.45 Ci mmol⁻¹ (16.7 TBq mol⁻¹) and 4.4 Ci mmol⁻¹ (0.16 PBq mol⁻¹), respectively, and with the purity exceeding 98%.