1082745-50-3

1082745-49-0

1082745-50-3

General procedure for the synthesis of 5-amino-1-(tetrahydro-pyran-4-yl)-1H-pyrazole-4-carbonitrile as 5-amino-1-(tetrahydro-pyran-4-yl)-1H-pyrazole-4-carboxylic acid amide: 5-amino-1-(tetrahydro-pyran-4-yl)-1H-pyrazole-4-carbonitrile (<228 mmol, the crude product from the previous reaction) was dissolved in ethanol ( 300 mL) in a 35% aqueous hydrogen peroxide solution (100 mL) and concentrated ammonia (300 mL) were added sequentially. The reaction mixture was stirred at room temperature for 48 h. The reaction was subsequently quenched with saturated aqueous sodium thiosulfate solution (800 mL). Ethanol was removed by distillation under reduced pressure and the resulting solid was separated by filtration and washed with water (2 x 200 mL) and ether (2 x 150 mL) to afford 5-amino-1-(tetrahydro-pyran-4-yl)-1H-pyrazole-4-carboxylic acid amide (31 g, 147 mmol). The overall yield of the two-step reaction from the starting material to the target product was 64%.ESI-MS (M-H)-: 211 (calculated value C9H14N4O2: 210.1).