Functionalization of 2,4-Dichloropyrimidines by 2,2,6,6-Tetramethylpiperidyl Zinc Base Enables Modular Synthesis of Antimalarial Diaminopyrimidine P218 and Analogues.

Two routes to the antimalarial diaminopyrimidine P218 were developed based on the C-6 metalation of suitable 2,4-dichloro-5-alkoxy pyrimidines using (TMP) 2 Zn·2MgCl 2 ·2LiCl base. One approach involves a late-stage modification of the C-6 position, while the other allows for tail fragment modification of P218 . Both routes have proven reliable in synthesizing P218 , as well as eight analogues. These innovative strategies have the potential to contribute to the search for new antimalarial drugs.