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 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.
Njoroge
F. George
FG
Schering-Plough Research Institute, Department of Chemistry, 2015 Galloping Hill Road, Kenilworth, New Jersey, 07033.
Vibulbhan
Bancha
B
Pinto
Patrick
P
Chan
Tze-Ming
TM
Osterman
Rebecca
R
Remiszewski
Stacy
S
Del Rosario
Jocelyn
J
Doll
Ronald
R
Girijavallabhan
V.
V
Ganguly
Ashit K.
AK