Development of a Synthesis of a 2,3-Disubstituted 4,7-Diazaindole Including Large-Scale Application of CH3Li/TiCl4-Mediated Methylation of an Enolizable Ketone

The chemical development of a 2,3-disubstituted 4,7-diazaindole is described. The requisite tertiary carbinol substrate was prepared employing in situ-generated CH3TiCl3 as a chemoselective and preferred reagent compared to CH3MgX for methyl addition to an enolizable ketone. The 4,7-diazaindole ring system was efficiently assembled via an intramolecular Chichibabin transformation. The optimized processes were performed on pilot-plant scale to provide kilogram quantities of the target molecule.