4-Amino-1-methylpyrazole

par flask was charged with 1-methyl-4-nitro-1H-pyrazole 15 (5.3 g, 41.0 mmol) and methanol (70 mL) followed by addition of Pd-C (50percent w/w, 2.70 g). The flask was evacuated under vacuum and then purged with hydrogen. The reaction was stirred under hydrogen atmosphere (30 psi). The reaction was monitored by TLC. It was then filtered through sintered funnel with a pad of celite, washed with methanol and concentrated under reduced pressure to afford precursor-05 as a brown colored gummy solid (4.0 g, 99percent yield) that was used as such for the next step without any further purification. ‘H NMR (400 MHz, CDC13): 6 7.12 (s, 1H), 6.97 (s, IH), 3.78 (s, 3H), 2.87 (br s, 2H).Under hydrogen (1 atm), to a solution of compound 15-b (1.0 g, 7.87 mmol) in ethanol (15 mL) was added 10percent Pd—C (0.2 g). The mixture was stirred at 25° C. for 18 hours, and then filtrated, the filtrate was concentrated under reduced pressure, the residue was purified by silica column chromatography (petroleum ether:ethyl acetate=1:1) to give red oil 15-a (700 mg, yield: 92percent).Pd / C (10percent, 500 mg) was added to the column1-methyl-4-nitro-1H-pyrazole (1.90 g, 14.9 mmol)And methanol (25 mL)Hydrogen at room temperature overnight.Diatomaceous earth filter, dichloromethane washing filter cake, The filtrate was concentrated under reduced pressure, (Eluent: ethyl acetate / methanol (v / v) = 18/1) to give 1.35 g of a black solid, yield:83.7percent.Step 1: 1-Methyl-1H-pyrazol-4-amine[2226]To 10 mL of methanol were added 1-methyl-4-nitro-1H-pyrazole (500 mg, 3.93 mmol) and Pd/C (10, 50 mg) . The mixture was stirred at rt for 6 hours under hydrogen atomosphere at ordinary pressure, then filtered. The filtrate was concentrated to give red liquid (305 mg, 80) .[2227]Example 25Synthesis of 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-N-(1-methyl-1H-pyrazol-4-yl)-6-(4-morpholinyl)-1, 3, 5-triazin-2-amineThe compound was synthesized according to Method A.A mixture of 0.996 g (8.82 mmol) of 4-nitropyrazole (J. Med. Chem. 2005, 48, 5780-5793) and 1.33 g (10.6 mmol) of dimethyl sulphate in 10 mL of 1 M NaOH was heated at 35° C. for 48 hrs. The reaction mixture was cooled to RT and the precipitate was filtered, washed with water, and dried to give 0.561 g (50percent yield) of 1-methyl-4-nitro-1H-pyrazole:

Molecular Weight:97.12
XLogP3:-0.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:97.063997236
Monoisotopic Mass:97.063997236
Topological Polar Surface Area:43.8
Heavy Atom Count:7
Complexity:64
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes