The general procedure for the synthesis of 5-amino-1-isopropyl-1H-pyrazole-4-carbonitrile from isopropylhydrazine dihydrochloride and ethoxymethylene malononitrile was as follows: ethoxymethylene malonitrile (12.83 g, 105 mmol) and isopropylhydrazine hydrochloride (11.06 g, 100 mmol) were dissolved in ethanol (250 mL). Subsequently, diisopropylethylamine (36.6 mL, 210 mmol) was added slowly and the temperature of the reaction mixture was increased. The reaction was continuously stirred at room temperature for about 18 hours. Upon completion of the reaction, the volatiles were removed by distillation under reduced pressure and the viscous yellow oil obtained was dissolved in dichloromethane and purified by a short silica gel column. The elution was first performed with dichloromethane (~300 mL) followed by a solvent mixture of ethyl acetate and hexane (1:1, ~750 mL). The eluate containing the target product was collected and concentrated under reduced pressure to give 5-amino-1-isopropyl-1H-pyrazole-4-carbonitrile (C20) as a light yellow solid. Yield: 12.1 g, 80.6 mmol, 81% yield.LC-MS m/z 151.1 (M + 1).1H NMR (400 MHz, DMSO-d6) δ 1.26 (d, J = 6.6 Hz, 6H), 4.41 (heptadecameric peaks, J = 6.5 Hz, 1H), 6.52 (broad single peak, 2H), 7.53 (single peak, 1H).
