Methylamine → 5-Methyl-2-nitro-4,5,6,7-tetrahydropyrazolo[1,5-A]pyrazine

To a solution of 1-(2-bromoethyl)-5-(bromomethyl)-3-nitro-1H-pyrazole (469 mg, 1.5 mmol) in tetrahydrofuran (20 mL) was added methylamine (2.0M in tetrahydrofuran, 5.25 mL, 10.5 mmol) drop wise and the resulting mixture was stirred at room temperature for 76 h. The solution was concentrated and the resulting solid was stirred with a mixture of ethyl acetate (10 mL) and 10% aqueous potassium carbonate (10 mL). The layers were separated and the aqueous phase was extracted with ethyl acetate (2×30 mL). The organic layers were combined and dried over magnesium sulfate. The resulting mixture was filtered and reduced in volume in vacuo and the precipitate removed by filtration. The filtrate was concentrated and the residue purified by flash chromatography (silica gel, 12 g, 2% to 10% methanol in dichloromethane) to give 5-methyl-2-nitro-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrazine (67 mg, 24%) as a light yellow solid.