Antiviral drug nevirapine as a template for hydrated imidazoline ring expansion (HIRE): Rapid access to the diarene-fused 1,4,7-triazecine ring system

The tricyclic ring system of the antiviral drug nevirapine has been employed to test the workability of the hydrated imidazoline ring expansion (HIRE) reaction which was previously exemplified for [1.4]oxazepine and [1.4]thiazepine counterparts. The imidazoline nucleus was grafted onto the lactam moiety of nevirapine in two high-yielding steps. Subsequent N-alkylation and the HIRE reaction proceeded as envisioned and delivered rare ring-expanded diarene-fused 1,4,7-triazecines with a diversity of alkyl substituents at the lactam nitrogen atom. These findings extend the scope of the HIRE reaction to the medicinally prominent [1.4]diazepine chemical space.