Development of an Efficient Synthesis of an Agonist of Acetylcholine Nicotinic Receptor

A new manufacturing process for N -[[1-(methylamino)cyclopropyl]methyl]pyridine-3-amine hemigalactarate ( 1 ) has been developed. Herein we wish to report the development and optimization of the route using alternative reaction conditions for a reduction/oxidation/reductive amination/protecting group cleavage sequence. Improvement of the crystallization process enabled the production of multikilogram amounts of agonist 1 under cGMP control with a purity of >99.5%. A telescoped process involving 5 steps is also described.