[Synthesis]
General procedure for the synthesis of 5-amino-1-(4-(methylsulfonyl)phenyl)-1H-pyrazole-4-carbonitrile from ethoxymethylenemalonononitrile: 4-(methylsulfonyl)phenylhydrazine hydrochloride (2 g, 9 mmol) and sodium methanol (0.49 g, 9 mmol) were added to a 100 mL round-bottomed flask equipped with a reflux condenser and an N2 inlet septum. Methanol (20 mL) was added to the reaction flask under nitrogen protection and stirred at room temperature for 15-20 min until the purple color disappeared and a white precipitate formed. Subsequently, ethoxymethylene malononitrile (1.1 g, 9 mmol) was added and stirring was continued for 10 min at room temperature, followed by heating and refluxing for 150 min. After completion of the reaction, the reaction mixture was cooled, filtered and concentrated under reduced pressure to give the crude product. The solid residue was dissolved in a mixed solvent of ethyl acetate (EtOAc) and water, and the organic layer was separated, washed with saturated aqueous sodium chloride (NaCl), dried over anhydrous sodium sulfate (Na2SO4), and concentrated to give the second part of the crude product. The crude product was purified by fast chromatography (eluent: 10% methanol/dichloromethane) and recrystallized from methanol to give a yellow crystalline product (625 mg, 26% yield). The structure of the product was confirmed by 1H NMR (DMSO-D6, 400 MHz): δ 3.27 (s, 3H), 6.98 (s, 2H), 7.81 (d, 2H), 7.88 (s, 1H), 8.06 (s, 2H).The LCMS analysis: the calculated value of C11H10N4O2S was 262.05 and the measured value was 262.9 (MH+). |