Trifluoroacetic acid → 4-(4-chloro-2-methoxyphenyl)-N-(1,2,4-thiadiazol-5-yl)quinazoline-7-sulfonamide

Participants

Reaction Steps

A solution of N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine (0.112 g, 0.445 mmol) in tetrahydrofuran (1.780 ml) was cooled in a dry ice-acetone bath for 5 min. Lithium bis(trimethylsilyl)amide (1M in THF) (0.490 ml, 0.490 mmol) was added drop wise, then the flask was removed from the cooling bath for 5 min. The flask was again cooled into a dry ice-acetone bath for 20 min, resulting in the formation of a thick slurry. A solution of perfluorophenyl 4-(4-chloro-2-methoxyphenyl)quinazoline-7-sulfonate (Intermediate AAAAAA; 0.230 g, 0.445 mmol) in THF (1.5 mL) was added drop wise, and the reaction was stirred for two hours. The reaction was warmed to room temperature and quenched with saturated ammonium chloride solution, diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The filtrate was purified by chromatography on an 12-g Redi-Sep Gold column with 0-50% EtOAc/Heptane. The material was dissolved in DCM and TFA (0.1 ml, 1.298 mmol) was added. The reaction was stirred for 30 minutes at room temperature. The reaction was concentrated and purified via column chromatography (RediSep Gold 12 g, gradient elution 0-10% MeOH:DCM) to afford 4-(4-chloro-2-methoxyphenyl)-N-(1,2,4-thiadiazol-5-yl)quinazoline-7-sulfonamide as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=9.48 (s, 1H), 8.49 (s, 1H), 8.40 (d, J=1.6 Hz, 1H), 7.97 (dd, J=1.8, 8.7 Hz, 1H), 7.87 (d, J=8.8 Hz, 1H), 7.47 (d, J=8.1 Hz, 1H), 7.39 (d, J=1.7 Hz, 1H), 7.25 (dd, J=1.8, 8.1 Hz, 1H), 3.72 (s, 3H). m/z (ESI) 434.0 (M+H)+.

Provenance & Evidence