Synthesis of the 8-aminoquinoline antimalarial 5-fluoroprimaquine

Article abstract of DOI:10.1016/S0040-4020(98)00177-X

Several approaches to the synthesis of 5-fluoro-6-methoxy-8- nitroquinoline 5, the key intermediate required for the synthesis of 5- fluoroprimaquine, were investigated. In one approach, 5chloro-6-methoxy-8- nitroquinoline was synthesised and treated with a variety of nucleophilic sources of fluoride. In another approach, electrophilic substitution of 6- methoxy-8-nitroquinoline with (N-fluorosulfonimide, NFSI) was investigated. The final approach to 5 involved a modified Skraup reaction of 5-fluoro-4- methoxy-2-nitroaniline which gave the required intermediate in 30% yield.