Synthesis of C-11 Methyl-Substituted Benzocycloheptapyridine Inhibitors of Farnesyl Protein Transferase

[formula: see text] Synthesis of C-11 methyl-substituted benzocycloheptylpyridine tricyclic compounds has been achieved via two different methods. Methylation of C-11 has been effected by treatment of amine 4 with BuLi followed by Mel quenching. In a similar procedure, introduction of a C-11 substituent with concomitant rearrangement of the exocyclic double bond has been carried out. Potent farnesyl protein transferase inhibitors have been synthesized using the above methodologies.