Concise approach for the synthesis of Voxelotor for sickle cell disease

Abstract

A novel approach has been developed for the synthesis of Voxelotor, which is used for the treatment of Sickle Cell Disease (SCD). The key steps involved in this approach are the ring opening of 2,3-pyridinedicarboxylic anhydride with isopropanol, the formation of pyrazole ring from N,N-dimethylenamino ketone and hydrazine.hydrate, the regioselective N-isopropylation of pyrazole ring and the O-alkylation of 2,6-dihydroxybenzaldehyde. Alternatively, a protecting group free approach for the synthesis of key intermediates 8 and 14 of Voxelotor has been developed.