Process Development for the Synthesis of a Selective M1 and M4 Muscarinic Acetylcholine Receptors Agonist

A practical and chromatography-free synthetic process to selective M1 and M4 muscarinic acetylcholine receptors agonist was developed and demonstrated on a several hundred gram scale. The key feature of this route is N,N-dimethylcarbamoylation of the anilinic nitrogen on the spiro 7-azaindoline structure via intermolecular migration of the N,N-dimethylcarbamoyl group. The resulting compound 1 was prepared in 43% overall yield with a chemical purity >99% via six steps starting with (2-chloropyridin-3-yl)acetonitrile.