Triphenylphosphine → HCID 67546639, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-hydroxy-isothiochroman-7-carbonitrile, which can be prepared as described in Example 12, (300 mg, 1.6 mmol) in THF (20 mL) is added (3H-imidazol-4-yl)-pyrrolidin-1-yl-methanone (200 mg, 1.2 mmol), and triphenylphosphine (420 mg, 1.6 mmol). The reaction is cooled to 0° C. and diisopropyl azodicarboxylate (310 μL, 1.6 mmol) is added. The reaction is permitted to warm to room temperature and stirred until LC-MS analysis indicates complete consumption of 4-hydroxy-isothiochroman-7-carbonitrile. The reaction mixture is diluted with saturated aqueous NaHCO3 and ethyl acetate. The layers are separated and the organic layer is dried with Na2SO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 1:1) to afford 4-[5-(Pyrrolidine-1-carbonyl)-imidazol-1-yl]-isothiochroman-7-carbonitrile; MS: (ESI) m/z 339.2 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 1.88-2.08 (m, 4 H), 3.17-3.37 (m, 2 H), 3.53-3.68 (m, 2 H), 3.69-3.77 (m, 2 H), 3.79-3.98 (m, 2 H), 6.55 (t, J=4.6 Hz, 1 H), 7.19 (d, J=8.1 Hz, 1 H), 7.39 (s, 1 H), 7.43-7.48 (m, 2 H), 7.50 (s, 1 H). The HCl salt of the title compound can be prepared by dissolution in diethyl ether followed by treatment with an excess of 1N HCl in diethyl ether. The resulting heterogeneous solution is concentrated to furnish the HCl salt of 4-[5-(Pyrrolidine-1-carbonyl)-imidazol-1-yl]-isothiochroman-7-carbonitrile.

Provenance & Evidence