Synthesis of [ 14 C]‐radiolabelled entecavir

Radiolabelled [ 14 C]entecavir, ( 1 ), was prepared in 12 steps from (1S,2R,3S,5R)‐3‐(benzyloxy)‐2‐(benzyloxymethyl)‐6‐oxa‐bicyclo[3.1.0]hexane 2 . The chemical yield of [ 14 C]entecavir was 14% from the epoxide 2 . Introduction of [ 14 C] radiolabel was achieved by elaboration of 4,5‐diaminopyrimidine 8 with triethyl[ 14 C]orthoformate to purine derivative 9 . The radiochemical yield of [ 14 C]entecavir from triethyl[ 14 C]orthoformate was 11.3%. Radiochemical purity of [ 14 C]entecavir determined by HPLC was 99.8%. The specific activity of [ 14 C]entecavir was 108 µCi/mg (29.9 mCi/mmol). Copyright © 2005 John Wiley & Sons, Ltd.