Potassium thiocyanate → (R)-N-benzyl-N-(2-(3-(6,8-difluorochroman-3-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-yl)ethyl)-2-nitrobenzenesulfonamide

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Reaction Conditions

Reaction Steps

To a mixture of (R)-6,8-difluorochroman-3-amine(2R,3R)-2,3-dihydroxysuccinate (compound JT′, 1.7 g, 5.07 mmol), N-benzyl-N-(4-hydroxy-3-oxobutyl)-2-nitrobenzenesulfonamide (compound I, 2.303 g, 6.08 mmol) in acetic acid (12.5 ml) was added potassium thiocyanate (0.591 g, 6.08 mmol) in one portion. The mixture was heated with stirring at 100° C. for 3 hours under HPLC control, cooled to 20° C., diluted with 2-propanol (55 ml), cooled to 0° C., aged for 1 hour. The precipitate collected, washed with cold 2-propanol (55 ml), dried to give 12.54 g. The solid was suspended in a mixture of water (38 ml) and ethanol (EtOH) (19 ml), solid sodium bicarbonate (2.255 g, 26.8 mmol) was added in portions with stirring at 20-25° C., stirred for 30 min. Solid collected, washed with water, dried to give (R)—N-benzyl-N-(2-(3-(6,8-difluorochroman-3-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-yl)ethyl)-2-nitrobenzenesulfonamide (compound K′, 8.4 g, 14.32 mmol, 64.0% yield).

Provenance & Evidence