A facile synthesis of bis-tacrine isosteres

An efficient synthesis of highly potent and selective acetylcholinesterase (AChE) inhibitors, bis-tacrines and their isosteres 2–4, has been accomplished by bis-amination of 9-chloro-tetrahydroacridine (9a) and its analogs. The critical intermediates were concisely prepared in situ by heating the corresponding ortho-amino aromatic acids and cycloketones in the presence of phosphorus oxychloride.