Resonance-assisted amide protonation in dutasteride hydrochloride salt

Abstract

Two novel crystal structures of dutasteride (hemihydrate and hydrochloride salt, crystallised before and after protonation respectively) are presented. Interestingly, in the dutasteride salt, only cyclic amide was protonated, but not phenyl amide. The protonation is attributed to increase in the amide resonance that results in significant increase in the acceptor strength (or basicity) of amide O.