A scalable process for the synthesis of key intermediates novoldiamine & hydroxynovaldiamine and their utility in chloroquine, hydroxychloroquine and mepacrine synthesis

A highly efficient and scalable process for the synthesis of novoldiamine and hydroxynovaldiamine is accomplished from levulinic acid, which is easily accessible from the natural feedstock. These diamines are used as the key intermediates for the synthesis of chloroquine, hydroxychloroquine and mepacrine. The key steps involved in this process are the coupling of levulinic acid with secondary amine assisted by 1, 1'-carbonyldiimidazole and one-pot reduction of oxime-amide functional groups to get the corresponding diamine.

Automated summary

A highly efficient and scalable process for the synthesis of novoldiamine and hydroxynovaldiamine from levulinic acid has been achieved. These compounds are crucial intermediates for the synthesis of antimalarial drugs chloroquine, hydroxychloroquine, and mepacrine.