4-AMINO-1-ISOPROPYL-1H-PYRAZOLE

Into a 25 mL round-bottom flask were placed a solution of intermediate 53.3 (200 mg, 1.29 mmol, 1.00 equiv) in methanol (4 mL) and palladium on charcoal (40 mg). To the above mixture H2 (g) was introduced, and the reaction was stirred for 3 h at room temperature. The solids were filtered and resulting filtrate was concentrated under vacuum to provide 154 mg (95percent) of intermediate 53.3 as pink oil.Under hydrogen (1 atm), to a solution of compound 41-b (1.1 g, 8.8 mmol) in ethanol (20 mL) was added 10percent Pd—C (0.2 g). The mixture was stirred at 25° C. for 12 hours, and then filtrated, the filtrate was concentrated under reduced pressure to give compound 41-a (830 mg, yield: 94percent), which was used directly for the next step without purification. LC-MS (ESI): m/z=126 [M+H]Synthesis of Compound 6.2. Into a 500-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed 4-nitro-l-(propan-2-yl)-lH- pyrazole (6.1) (3.0 g, 19.34 mmol, 1.00 equiv), palladium on carbon (200 mg), and methanol (250 mL). The flask was evacuated and flushed three times with nitrogen, followed by flushing with hydrogen. The mixture was stirred 2 h at room temperature under an atmosphere of hydrogen (balloon). The resulting solution was stirred for 2 h at room temperature. The solids were filtered off. Then the resulting mixture was concentrated in vacuo. This provided 2.2 g (91percent) of l-(propan-2-yl)-lH-pyrazol-4-amine (6.2) as red oil.