Pilot plant production of Anti-malarial Drug piperaquine phosphate and synthesis of its metabolites

An optimized, convergent, safe synthesis of piperaquine phosphate (1), an antimalarial agent, as well as synthesis of its main metabolites was described. Major improvements for piperaquine phosphate (1) production were made in the preparation of intermediate 7 by using directly piperazine instead of N-formyl piperazine. The structures of the synthetic compounds were determined from spectral analysis including MS and 2D NMR.