Synthesis of double carbon‐14 labeled CI‐937 1 and CI‐942, potential new anticancer drugs

CI‐937 and CI‐942, compounds which show potent anticancer activity, were synthesized with double labeled high specific activity carbon‐14. The key intermdiate in the synthesis, 3,6‐dichloro‐[dicarbonyl‐ 14 C 2 ]phthalic anhydride was made by treating 2‐bromo‐1,4‐dichlorobenzene with n‐butyllithium and 14 CO 2 to give 2,5‐dichloro[carboxy‐ 14 C]benzoic acid, which was converted to its diethylamide. Ortho‐directed lithiation followed by a second carboxylation produced the ortho acid‐amide. Hydrolysis and dehydration generated the anhydride. Friedel‐Crafts acylation of the anhydride with 1,4‐benzenediol gave 1,4‐dichloro‐5,8‐dihydroxy[9,10‐ 14 C 2 ]‐9,10‐anthracenedione. Protection and hydrazination gave a chloroanthrapyrazole intermediate which was converted into [ 14 C 2 ]CI‐937 or [ 14 C 2 ]CI‐942 in two steps. The specific activities of the final compounds were 196 μCi/mg and 182 μCi/mg respectively.