Triphenylphosphine Oxide → N-[5-(4,5-dihydro-1,3-thiazol-2-yl)-1-ethyl-1,4-dihydropyrrolo[3,2-b]pyrrol-3-yl]-N-methylthiophene-2-sulfonamide

Participants

Reaction Steps

To a mixture of 4-ethyl-6-[methyl(2-thienylsulfonyl)amino]-1,4-dihydropyrrolo[3,2-b]pyrrole-2-carboxylic acid (780 mg), 2-(tritylthio)ethaneamine hydrochloride (850 mg), 1H-1,2,3-benzotriazol-1-ol (370 mg), triethylamine (0.5 mL) and N,N-dimethylformamide (15 mL) was added N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (460 mg), and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated to give a colorless oil. To a solution of triphenylphosphine oxide (1.8 g) in dichloromethane (20 mL) was slowly added trifluoromethanesulfonic anhydride (555 μL) at 0° C., the mixture was stirred for 10 min, and the colorless oil was added. The reaction mixture was stirred at room temperature for 2 hr and concentrated. Saturated aqueous sodium hydrogen carbonate was added thereto, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography to give N-[5-(4,5-dihydro-1,3-thiazol-2-yl)-1-ethyl-1,4-dihydropyrrolo[3,2-b]pyrrol-3-yl]-N-methylthiophene-2-sulfonamide (260 mg, yield 30%) as colorless crystals from a fraction eluted with ethyl acetate-hexane (1:20 to 1:3, volume ratio). melting point 163° C.

Provenance & Evidence