Highly Regioselective Nitration Reactions Provide a Versatile Method of Functionalizing Benzocycloheptapyridine Tricyclic Ring Systems: Application toward Preparation of Nanomolar Inhibitors of Farnesyl Protein Transferase

F. George Njoroge; Bancha Vibulbhan; Patrick Pinto; Tze-Ming Chan; Rebecca Osterman; Stacy Remiszewski; Jocelyn Del Rosario; Ronald Doll; V. Girijavallabhan; Ashit K. Ganguly

doi:10.1021/jo971100z

Highly Regioselective Nitration Reactions Provide a Versatile Method of Functionalizing Benzocycloheptapyridine Tricyclic Ring Systems: Application toward Preparation of Nanomolar Inhibitors of Farnesyl Protein Transferase

J Org Chem. 1998 Feb 6;63(3):445-451. doi: 10.1021/jo971100z.

Authors

F. George Njoroge¹, Bancha Vibulbhan, Patrick Pinto, Tze-Ming Chan, Rebecca Osterman, Stacy Remiszewski, Jocelyn Del Rosario, Ronald Doll, V. Girijavallabhan, Ashit K. Ganguly

Affiliation

¹ Schering-Plough Research Institute, Department of Chemistry, 2015 Galloping Hill Road, Kenilworth, New Jersey, 07033.

PMID: 11672031
DOI: 10.1021/jo971100z

Abstract

A comprehensive study of nitration reaction of azatricyclic systems has been carried out. Whereas classical nitrations using KNO(3)-H(2)SO(4) at low temperatures gave nitrated products mainly at the 9-position, use of tetrabutylammonium nitrate-trifluoroacetic anhydride (TBAN-TFAA) resulted in exclusive nitration of the 3-position in the case carbamates 1, and 4-6 and the tricyclic ketone 7. These 3-nitro tricyclic derivatives have been valuable intermediates for the preparation of the very potent farnesyl protein transferase inhibitors such as the tricyclic pyridyl acetamide 32 and other new analogues.