Synthesis of morpholinium [13C] formate and its application in the synthesis of [8‐13C] purine base

Morpholinium [13C]formate is obtained by neutralizing an aqueous solution of equivalent amounts of sodium [13C]formate and hydrochloric acid with morpholine. Morpholinium [13C]formate is isolated in crystalline form and characterized. Treatment of 6‐hydroxy‐2,4,5‐triaminopyrimidine sulfate with morpholinium [13C]formate at 200° affords [8‐13C]guanine in 80% yield. There is no necessity to synthesize and isolate [13C]‐N‐formylmorpholine and the intermediate N5‐[13C]formyl pyrimidine derivative. Mass spectrometric analysis shows that the molar isotopic concentration of 13C label in guanine is identical to that of the morpholinium [13C]formate and there is no isotopic scrambling. The same procedure when used with 4,5,6‐triaminopyrimidine sulfate affords adenine in 85% yield.