Anisole → HCID 71557176, compound

Participants

Reaction Steps

To a solution of 4-(4-chloro-2-(7-(4-methoxybenzyl)-8-oxo-7,8-dihydroimidazo[1,5-a]pyrazin-5-yl)phenoxy)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (0.20 g, 0.25 mmol) and anisole (0.54 mL, 5.0 mmol) in trifluoroacetic acid (2 mL) at 0° C. was added trifluoromethanesulfonic acid (0.22 mL, 2.5 mmol). The reaction mixture was allowed to warm to ambient temperature, stirred for 16 h and concentrated in vacuo. The residue was partitioned between dichloromethane (30 mL) and saturated aqueous sodium bicarbonate (30 mL). The aqueous phase was washed with dichloromethane (2×30 mL), acidified to pH 3-4 with 1 M hydrochloric acid and extracted with ethyl acetate (5×40 mL). The combined ethyl acetate extracts were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was triturated in ethyl acetate/diethyl ether (5/95 v/v) to afford 4-(4-chloro-2-(8-oxo-7,8-dihydroimidazo[1,5-a]pyrazin-5-yl)phenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide as an off-white solid in 77% yield (0.104 g): 1H NMR (300 MHz, DMSO-d6) δ11.22 (d, J=4.8 Hz, 1H), 8.55 (s, 1H), 8.49 (br s, 1H), 8.11 (br s, 1H), 7.80 (s, 1H), 7.76-7.63 (m, 2H), 7.41-7.29 (m, 2H), 6.95 (d, J=5.3 Hz, 1H); MS (ES+) m/z 536.7 (M+1), 538.7 (M+1).

Provenance & Evidence