Synthesis of 3H and 14C labelled changrolin

3 kinds of [14C] and [3H] changrolin labelled at different positions (I, II, III) were prepared. The synthesis of I is as follows: (Scheme 1): Heating 5-bromoanthranilic acid with formamide yielded IV, which on heating with POCl3 gave V. Condensation of V with 4-aminophenol and Mannich reaction produced 6-bromochangrolin (VI). Catalytic dehalogenation of VI with tritium gas gave I. The synthesis of II was started from (14C) formamide and anthranilic acid. Labelled 4-chloroquine obtained was condensed with Mannich base (VII) directly (Scheme 2). III was prepared by 1 step with (14C) formaldehyde (Scheme 1)