Optimized synthesis of tetrahydroisoquinoline-hydantoins

Abstract 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.