Solid phase synthesis of cyanoacetamidines: Fast access to potential bioisosteres of acceptor-substituted guanidines

A synthesis of cyanoacetamidines has been developed, which can be realized on solid support. Reaction of resin-bound cyanoacetic acid with aromatic isothiocyanates yielded thioamides, which could be condensed with primary or secondary aliphatic or aromatic amines in the presence of EDC to yield ketene aminals, TFA-mediated cleavage from the support with concomitant decarboxylation gave cyanoacetamidine trifluoroacetates in purities up to 83% (HPLC, 254 nm). (C) 1997 Elsevier Science Ltd.