A new synthesis of substituted acridine-4-carboxylic acids and the anticancer drug N-[2-dimethylamino)ethyl]acridine-4-carboxamide (DACA)

Article abstract of DOI:10.1016/S0040-4039(96)02396-9

A new synthesis of substituted acridine-4-carboxylic acids 2 from methyl 2-[N-(2-carboxyphenyl)amino]benzoates (4) is reported, via NaBH₄ reduction of the corresponding imidazolides (5), oxidation of the resulting alcohols 6 to aldehyde 7, and cyclisation of these with trifluoroacetic acid to the methyl acridine-4-carboxylates (8), followed by base hydrolysis. Direct amidation of 8a provides a new route to the clinical anticancer drug DACA (3) which avoids use of the irritant acid 2a.