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.

1. concentrationThe solution was concentrated
2. stirringthe resulting solid was stirred with a mixture of ethyl acetate (10 mL) and 10% aqueous potassium carbonate (10 mL)
3. customThe layers were separated
4. extractionthe aqueous phase was extracted with ethyl acetate (2×30 mL)
5. dry with materialdried over magnesium sulfate
6. filtrationThe resulting mixture was filtered
7. customthe precipitate removed by filtration
8. concentrationThe filtrate was concentrated
9. customthe residue purified by flash chromatography (silica gel, 12 g, 2% to 10% methanol in dichloromethane)

ORD record

ord-40220d7965374ea39b4ca9cd0b6f3a14

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08940741B2