Synthesis of 2-methylcarbamazepine, a new internal standard for chromatographic assays of carbamazepine (Tegretol)

Article abstract of DOI:10.1002/jhet.5570160213

The synthesis of 2-methyl-5H-dibenz[b,f]azepine-5-carboxamide (2-methylcarbamazepine, 2-MCBZ), a promising internal standard for chromatographic assays of the antiepileptic agent carbamazepine is described. N-(p-tolyl)anthranilic acid was utilized as a starting material for the synthesis of a key compound, 2,9-dimethylacridine, which was converted in two steps to 2-methyl-9-hydroxymethylacridan. The acridan, in the presence of polyphosphoric acid, was ring-expanded to form 2-methyl-5H-dibenz[b,f]azepine, this latter compound being converted by conventional reactions to its 5-carbamyl derivative, 2-MCBZ.