We imagined achieving these goals via a reordered sequence of bond-forming events which harness the pyrimidine's natural reactivity (Figure ). Introducing the piperazine early could be particularly beneficial. The northern aryl chloride presents itself as the pyrimidine's most reactive electrophile. Conducting the SNAr in this way eliminates 3 steps related to protection, demethylation, and activation at this locus. Moreover, a high-yielding transformation would resolve two particularly low-yielding operations. The synthesis would then revert to the established sequence of bond forming events (etherification  arylation  acylation).