Synthesis of [8‐14C]‐2,6‐dichloro‐9H‐purine, a radiolabelled precursor for 14C‐nucleosides

Abstract

AbstractThe synthesis of [8‐14C]‐2,6‐dichloro‐9H‐purine (2), a radiolabelled precursor for preparing 14C‐labelled nucleosides, is described. Triethyl[14C]orthoformate was reacted with 4,5‐diamino‐2,6‐dichloropyrimidine (1) in acetonitrile at 90°C with methanesulfonic acid as catalyst to generate 2 in 84% radiochemical yield. Reaction of 2 with 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐D‐ribofuranose produced [8‐14C]‐9‐(2,3,5‐tri‐O‐benzoyl‐β‐D‐ribofuranosyl)‐2,6‐dichloropurine (3) in 86% yield. The radiochemical purity of 3 was higher than 98% with a specific activity of 36 mCi/mmol. This method has general application to 14C‐labelling of purines in drug development.