A PRACTICAL SYNTHESIS OF FIBRINOGEN RECEPTOR ANTAGONIST MK-383 - SELECTIVE FUNCTIONALIZATION OF (S)-TYROSINE

A practical 4-step synthesis of fibrinogen receptor antagonist MK-383, ulfonyl)-O-(4-(4-piperidinyl)-butyl)-(S)-tyrosine, is accomplished in 48% overall yield from (S)-tyrosine. Highlights include: (1) the dual use of 4-picoline as a masked form of piperidine, and as a nucleophil e precursor for a 3 carbon homologation with 3-bromo-1-chloropropane; (2) the use of trimethylsilyl groups for temporary protection of pheno lic and carboxylate oxygens of (S)-tyrosine that enable selective N-su lfonylation to be carried out in high yield; (3) the selective phenoli c O-alkylation of the tyrosine derivative in high yield with no racemi zation using aqueous KOH/DMSO; and (4) the selective hydrogenation of the pyridine ring in the presence of the tyrosine ring using Pd/C in a cetic acid.