HIGHLY REGIOSELECTIVE NITRATION REACTIONS PROVIDE A VERSATILE METHOD OF FUNCTIONALIZING BENZOCYCLOHEPTAPYRIDINE TRICYCLIC RING-SYSTEMS - APPLICATION TOWARD PREPARATION OF NANOMOLAR INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE

A comprehensive study of nitration reaction of azatricyclic systems ha s been carried out. Whereas classical nitrations using KNO3-H2SO4 at l ow temperatures gave nitrated products mainly at the 9-position, use o f tetrabutylammonium nitrate-trifluoroacetic anhydride (TBAN-TFAA) res ulted in exclusive nitration of the 3-position in the case carbamates 1, and 4-6 and the tricyclic ketone 7. These 3-nitro tricyclic derivat ives have been valuable intermediates for the preparation of the very potent farnesyl protein transferase inhibitors such as the tricyclic p yridyl acetamide 32 and other new analogues.