Synthesis of N-(3-azido-4-chlorophenyl)-N'-[3H-methyl]thiourea, an efficient photoaffinity probe for the urea carrier

Article abstract of DOI:10.1002/jlcr.2580340312

Starting from commercial 4-chloro-3-nitroaniline, through a 5 step synthesis, was prepared 3-azido-4-chlorophenylisothiocyanate 5 which was reacted with [³H]-methylamine. The latter was obtained by three methods: i- [³H]-LiAlT₄ reduction of benzylcarbamate gave rise to [³H][-methylamine (S.A.: >70 Ci/mmol). ii- Catalytic reduction of HCN with ³H₂ lead to [³H]-CH₃NH₂ (S.A.: 0.7 Ci/mmol). iii- Schmidt rearrangement of [³H]-sodium acetate gave [³H]-CH₃NH₂ (S.A.: 29 Ci/mmol). Compound 7 at the highest specific activity had a self radiolysis rate precluding its practical use in biological studies whilst 29 Ci/mmol [³H]-7 was satisfactory.