An Improved Process for the Synthesis of 4H-Imidazo[1,5-a][1,4]benzo- diazepines An Improved Synthesis of 4H-Imidazo[1,5-a][1,4]benzodiazepines

Imidazo[1,5-a][1,4]benzodiazepines are well documented to exhibit potent activity at GABAA/Bz receptors. This series belongs to one of the very few chemical families, which have been extensively investigated for GABAA/Bz receptor mediated activity.1,2 Flumazenil (Ro 15-1788), an imidazo[1,5-a][1,4]benzodiazepine, was earlier shown to bind to central GABAA receptors with little or no intrinsic agonist activity, but with the ability to block the activity of an agonist or inverse agonist at GABAA/Bz receptors.2 It is employed principally as an antidote to reverse the effect of exogenous benzodiazepines.3 More recently ligands such as flumazenil have been shown to behave as weak inverse agonists or weak agonists depending on the biological paradigm employed. Many procedures have been reported to date to synthesize this imidazo-type of structure.4,5 Most of them have been achieved in low yield through an iminophosphate/ chloride intermediate.