The amidine is a privileged chemical motif as highlighted by both its prevalence within bioactive compounds, and its role as a key intermediate in the synthesis of heterocycles. While many methods towards their synthesis have been reported to date, recent reports have suffered either from the necessity of using solvent quantities of nitrile, or the use of trimethylaluminum, a reagent that poses a number of safety risks. This project highlights the use of magnesium ethoxide as an alternate reagent for this transformation, providing a mild, safe, and scalable reagent for intramolecular amidine cyclization. Further, we have demonstrated the utility of these amidine intermediates <i>via</i> direct treatment with chloroacetaldehyde to afford a variety of 5,6-dihydro-imidazobenzoazepines, a framework found in numerous medicinally relevant compounds. The outcome of this methodology is expected to have a broader impact within the pharmaceutical industry as it will provide an alternate reagent for both process and medicinal chemists to consider during development work.

Magnesium ethoxide promoted conversion of nitriles to amidines and its application in 5,6-dihydro-imidazobenzoxazepine synthesis

2019 Fall National Meeting

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