6-(Oxiran-2-yl)nicotinonitrile → 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)pyridine-3-carbonitrile

Participants

Reaction Conditions

Reaction Steps

To a microwave tube were added isomer B of 6-(oxiran-2-yl)pyridine-3-carbonitrile (330 mg, 2.26 mmol), 5-[(1R)-1-hydroxy-2-(piperazin-1-yl)ethyl]-4-methyl-2-benzofuran-1(3H)-one (686 mg, 2.48 mmol, as a free base), and EtOH (7.0 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 silica gel MPLC (0→10% CH2CH2:MeOH) 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)pyridine-3-carbonitrile as a single isomer. Further, the product was treated with 1 M HCl in diethyl ether to give the final product as an HCl salt. 1H NMR (500 MHz, DMSO-d6), δ 8.92 (s, 1H), 8.28 (dd, J=1.9 Hz, J=2.0 Hz, 1H), 7.68-7.63 (m, 3H), 5.48 (d, J=4.8 Hz, 1H), 5.37 (d, J=2.2 Hz, 2H), 5.20 (d, J=3.9 Hz, 1H), 5.03 (m, 1H), 4.78 (m, 1H), 2.64 (dd, J=4.1, 1H), 2.55-2.41 (m, 8H), 2.33 (dd, J=3.7 Hz, 1H), 2.24 (s, 3H); LC/MS: (IE, m/z) [(M+1)]+=423.04 (57A).

Provenance & Evidence