1-Methylpyrrolidine → 4-(2-(((3,3-Bis(4-fluorophenyl)propyl)(cyclopropyl)carbamoyl)amino)-5-chloro-1,3-thiazol-4-yl)benzenesulfonamide

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Reaction Steps

A solution of 4-(2-amino-5-chlorothiazol-4-yl)benzenesulfonamide (318 mg, 1097 μmol) and pyridine (266 μl, 3292 lμmol) in DMF (10 mL) was chilled to 0° C. To this solution was added slowly phenyl chloroformate (131 μl, 1043 μmol) via syringe. The mixture was slowly warmed to RT, and stirred for 2 hr. At this point, 1-methylpyrrolidine (342 μl, 3292 μmol) and N-(3,3-bis(4-fluorophenyl)propyl)cyclopropanamine hydrochloride (338 mg, 1043 μmol) were added consecutively to the reaction mixture. The mixture was heated to 80° C. and was stirred overnight. Volatiles were removed by concentration under reduced pressure. The leftover residue was solubilized with 100 mL of a 1:1 mixture of water and ethyl acetate. The organic phase was separated and the aqueous phase was extracted further with ethyl acetate (2×75 mL). The combined organic extracts were dried with magnesium sulfate, filtered, and concentrated. Purification by chromatography on silica (eluted with EtOAc/Hexanes) gave 4-(2-(((3,3-bis(4-fluorophenyl)propyl)(cyclopropyl)carbamoyl)amino)-5-chloro-1,3-thiazol-4-yl)benzenesulfonamide 182. Mass spectrum, calculated for C28H25ClF2N4O3S2 602. 1; found 603.1 (M++1).

Provenance & Evidence