Efficient synthesis of ribonucleotide reductase inhibitors 3- aminopyridine-2-carboxaldehyde thiosemicorbazone (3-AP) and 3-amino-4- methylpyridine-2-carboxaldehyde thiosemicarbazone (3-AMP) via palladium mediated cross-coupling reactions

Article abstract of DOI:10.1016/S0040-4020(97)10298-8

An efficient synthesis of potent ribonucleotide reductases inhibitors 3- amino-pyridine-2-carboxaldehyde thiosemicarbazone (3-AP) end 3-amino-4- methyl-pyridine-2-carboxaldehyde thiosemicarbazone (3-AMP) is described. The synthesis of 3-AP and 3-AMP was achieved in 4 and 5 steps, with overall yields of 61% and 39%, respectively. The synthesis featured a convergent approach utilizing a Stille coupling strategy to prepare vinylpyridine derivatives. A more economic way to synthesize vinylpyridine using Heck reaction was also discussed.