General procedure for the synthesis of 3-amino-5-cyclobutyl-1H-pyrazole from 3-cyclobutyl-3-oxopropanenitrile: Crude 3-cyclobutyl-3-oxopropanenitrile (10.0 g, 81.3 mmol) was dissolved in ethanol (300 mL), followed by addition of hydrazine in equimolar amounts. The reaction mixture was heated to 75 °C in an oil bath for 14 hours. Upon completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure. The concentrated oily product was dissolved in ethyl acetate and washed with saturated aqueous sodium bicarbonate. After separating the organic and aqueous layers, the aqueous layer was then extracted with ethyl acetate. All organic layers were combined, dried with anhydrous magnesium sulfate, filtered to remove the desiccant and the filtrate was concentrated under reduced pressure. The crude product was purified by rapid column chromatography on a Biotage 75S MPLC system (Dynax Corp., Charlottesville, VA), eluting sequentially with pure ethyl acetate (2 L) and 10% methanol/dichloromethane (2 L). The fraction containing the target product was collected and concentrated under reduced pressure to afford 3-amino-5-cyclobutyl-1H-pyrazole (10.0 g, 91% yield) as a brown oil. Its structure was confirmed by 400 MHz 1H NMR (CDCl3) and LRMS (APCI+): 1H NMR δ 5.47 (s, 1H), 5.25 (bs, 3H), 3.40 (dddd, J = 8.3,8.3,8.3,8.3, 8.3Hz, 1H), 2.34-2.27 (m, 2H), 2.16-1.88 (m. 4H); LRMS m/z (APCI+) 138 (M + 1).
