Chloroacetaldehyde → HCID 89544489, compound

Participants

Reaction Steps

To a stirred solution of 4-(2-(6-aminopyridin-2-yl)-4-chlorophenoxy)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (2.43 g, 3.75 mmol) in ethanol (75 mL) and water (9 mL) was added sodium bicarbonate (0.41 g, 4.9 mmol) and chloroacetaldehyde (50% w/w in water, 0.63 mL, 4.9 mmol) at ambient temperature. The mixture was heated at reflux for 16 h, allowed to cool to ambient temperature and diluted with dichloromethane (200 mL) and water (20 mL). The organic layer washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was dissolved in dichloromethane (50 mL) and trifluoroacetic acid (2 mL) was added. The reaction mixture was stirred for 5 h at ambient temperature and concentrated in vacuo. The residue was purified by column chromatography eluting with a 0-10% gradient of methanol in ethyl acetate to afford 4-(4-chloro-2-(imidazo[1,2-a]pyridin-5-yl)phenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide as a pale yellow solid in 43% yield (0.84 g): 1H NMR (300 MHz, DMSO-d6) δ8.14 (s, 1H), 7.93 (d, J=1.5 Hz, 2H), 7.87-7.78 (m, 2H), 7.76-7.66 (m, 2H), 7.62-7.52 (m, 1H), 7.42-7.30 (m, 3H); MS (ES+) m/z 519.8 (M+1), 521.8 (M+1).

Provenance & Evidence