Synthetic approach to condensed heterocyclic analogues from etoposide revisited. Synthesis of A-ring pyridazine etoposide

The synthetic approach to condensed heterocyclic analogues from etoposide was revisited. The described procedure allows the synthesis of A-ring pyridazine etoposide 13, featuring the use of tetrakis(triphenylphosphine)palladium as catalyst under optimized conditions in the key Stille cross coupling between bistriflate 14 and the vinylstannane without epimerization at C-2. The TBDMS-protecting group was critical to cleanly obtain the pivotal intermediate 19.