SYNTHESIS OF [8-C-14]-2,6-DICHLORO-9H-PURINE, A RADIOLABELED PRECURSOR FOR C-14 NUCLEOSIDES

The synthesis of [8-C-14]-2,6-dichloro-9H-purine (2), a radiolabelled precursor for preparing C-14-labelled nucleosides, is described. Triet hyl [C-14]orthoformate was reacted with 4,5-diamino-2,6-dichloropyrimi dine (1) in acetonitrile at 90 degrees 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 O-benzoyl-beta- D-ribofuranosyl)-2,6-dichloropurine (3) in 86% yield. The radiochemica l purity of 3 was higher than 98% with a specific activity of 36 mCi/m mol. This method has general application to C-14-labelling of purines in drug development.