Synthesis of 5-azacytidine-6-13C and -6-14C

5-Azacytidine (1) labeled with 13C or 14C at the chemically labile C-6 position was synthesized. A method utilizing hydrolytic opening of the triazine ring followed by recyclization with dimethylformamide dimethyl acetal was used. Urinary and biliary excretion was measured in rabbits following intravenous doses of 1-4-14C and 1-6-14C. Differences in recoveries of the dose from 4-14C and 6-14C demonstrate that ring cleavage of 1 with loss of the C-6 carbon represents a major metabolite route.