Synthesis of C-11 methyl-substituted benzocycloheptapyridine inhibitors offarnesyl protein transferase

[GRAPHICS] Synthesis of C-11 methyl-substituted benzocycloheptylpyridine tricyclic com pounds 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 concomitan t rearrangement of the exocyclic double bond has been carried out. Potent f arnesyl protein transferase inhibitors have been synthesized using the abov e methodologies.