Novel 4-aminoquinolines through microwave-assisted SNAr reactions : a practical route to antimalarial agents

4-Aminoquinolines have recently been indicated to be an important class of chemotherapeutic agents for artemisinin-based antimalarial combination therapy. A rapid, cheap, possibly clean and scalable route to 4-aminoquinolines endowed with multiple diversity is therefore badly needed. Classically, they have been prepared by means of SNAr reactions, requiring hazardous or costly reagents and conditions and complex purification procedures. In this paper, microwave flash-heating chemistry is shown to allow the efficient conversion of the available 4,7-dichloroquinoline into a library of aminoquinolines in high yields and purities, with no need for further purification steps and requiring very short reaction times. Some of the compounds in this library were active against chloroquine-sensitive and chloroquine-resistant parasite strains.