Several methods have been developed and compared for the solution synthesis of tetrahydroisoquinoline-hydantoin (Tic-hydantoin) derivatives. Starting materials were Tic-OH and amines readily available from commercial sources. The best yields were observed when the imidazolidine-2, 4-dione ring was synthesized in two steps:(1) reaction of Tic-OH with the appropriate amine and (2) cyclization with 1, 1′-carbonyldiimidazole.
