Synthesis of stable isotope–labeled chloroquine and amodiaquine and their metabolites

Anti‐malaria drugs chloroquine and amodiaquine and their metabolites were synthesized to incorporate ¹³C and ¹⁵N starting from U‐¹³C–labeled benzene to give M + 7 isotopomers. Chloroquine and its metabolites were prepared from 7‐chloro‐1,2,3,4‐tetrahydroquinolin‐4‐one through an aryl substitution with the corresponding amines; and the amodiaquine and its metabolites were prepared from 4,7‐dichloroquinoline in a similar fashion.