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

Abstract

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.

Graphical abstract

Keywords:

• Acid-amine coupling
• carbonyldiimidazole
• chloroquine
• hydroxychloroquine
• hydroxynovaldiamine
• mepacrine
• novoldiamine
• oxime synthesis
• reduction

Acknowledgements

N. K. C. and S. K. A. thank CSIR, New Delhi, for financial assistance in the form of fellowship. S. V. thanks ICMR for the financial assistance in the form of a fellowship. The authors thank director CSIR-IICT for his continuous encouragement. IICT communication no. IICT/Pubs./2021/383.