4-Methyl-6-(oxiran-2-yl)pyridine-3-carbonitrile → 6-(1-hydroxy-2-{4-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazin-1-yl}ethyl)-4-methylpyridine-3-carbonitrile

Participants

Reaction Conditions

Reaction Steps

To a microwave tube were added 4-methyl-6-(oxiran-2-yl)pyridine-3-carbonitrile (40 mg, 0.25 mmol), 5-[(1R)-1-hydroxy-2-(piperazin-1-yl)ethyl]-4-methyl-2-benzofuran-1(3H)-one (69 mg, 0.25 mmol, as a free base), and EtOH (3.0 mL). The mixture was heated in the microwave for 60 min at 140° C. The solvent was evaporated and the crude product was purified by chiral prep SFC (30% MeOH (0.1% DEA)/CO2 on OJ column) to provide 6-(1-hydroxy-2-{4-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazin-1-yl}ethyl)-4-methylpyridine-3-carbonitrile as individual isomers. Further, the products were treated with 1 M HCl in diethyl ether to give the final products as HCl salts.

Provenance & Evidence