Synthesis of benzothiophene analogues of ketoconazole and itraconazole

Article abstract of DOI:10.1002/jhet.5570340611

The synthesis of the benzothiophene analogues of the orally active antifungal agents ketoconazole and itraconazole 3a and 3b is reported. The key heterocyclic system 3-(1-piperazinyl)benzo[b]thiophene is prepared by formation of the enamine between a benzothienone and ethyl 1- piperazinecarboxylate. After elaboration of the respective N-substituents, the methoxy group is cleaved with boron tribromide, and O-alkylated with the corresponding mesylates.