The parasitic kinetoplastid diseases Leishmaniasis, Chagas disease and Human African Trypanosomiasis constitute serious threats for populations throughout the (sub‐)tropics. Most available drugs to treat these diseases possess inadequate properties and candidates to fill the drug pipeline are urgently needed. Paullone‐N⁵‐acetamides inhibit trypanothione synthetase (TryS), an essential kinetoplastid enzyme, and exhibit antiparasitic activity in the low micromolar range, but lack the desired selectivity against mammalian cells (selectivity index (SI):25).

(E)-5-(Methoxyimino)-1,3,4,5-tetrahydro-2H-benzo[b]azepin-2-one was prepared by a condensation reaction from 3,4-dihydro-1H-benzo[b]azepin-2,5-dione and O-methylhydroxylamine. The configuration at the C=N double bond was determined by X-ray crystallography.