3-cyano-4-fluoro-N-(thiazol-2-yl)benzenesulfonaMide synthesis

96-50-4

351003-23-1

1235406-28-6

General procedure for the synthesis of 3-cyano-4-fluoro-N-(thiazol-2-yl)benzenesulfonamide from 2-aminothiazole and 3-cyano-4-fluorobenzenesulfonyl chloride: 3-cyano-4-fluorobenzenesulfonyl chloride (10 g, 45.53 mmol) was added batchwise to a mixed solution of dichloromethane (50 mL) and pyridine (18.4 mL) containing 2-aminothiazole (5 g, 50.13 mmol) , 228 mmol) in a mixed solution. The reaction mixture was gradually warmed up to room temperature. After 1 hour of reaction, a precipitate was observed to be generated. The mixture was stirred continuously for 18 hours at room temperature. Subsequently, the mixture was sonicated for 2.5 hours until the solids were completely dissolved, after which stirring was continued for 18 hours at room temperature. Upon completion of the reaction, the mixture was concentrated under reduced pressure and azeotropically dried with toluene (2 x 100 mL) to remove residual water. The dried residue was carefully diluted with 1 M aqueous hydrochloric acid and stirred at room temperature for 1 hour to induce precipitate formation. The brown solid product was collected by filtration and purified by milling with dichloromethane to afford finally 3-cyano-4-fluoro-N-(thiazol-2-yl)benzenesulfonamide as a brown solid (7.8 g, 60% yield). The product was characterized by 1H NMR (d6-DMSO): δ 6.90 (m, 1H), 7.30 (m, 1H), 7.65 (t, 1H), 8.15 (m, 1H), 8.30 (m, 1H), 12.90 (br s, 1H).The results of the LCMS analysis were as follows: retention time Rt = 2.18 min, mass m/z 284 [MH]+, 282 [MH]-.