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

A 1-L Single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet was charged with THF (350 mL), 1-(2-bromoethyl)-5-(bromomethyl)-3-nitro-1H-pyrazole (10.0 g, 32.2 mmol), 2M methylamine solution in THF (113 mL, 225 mmol) and stirred at room temperature for 72 h. After this time the reaction was concentrated to dryness under reduced pressure, and the resulting solid was stirred with a mixture of ethyl acetate (75 mL) and 10% aqueous potassium carbonate (75 mL). The aqueous layer was separated and extracted with ethyl acetate (2×75 mL). The combined organic extracts were washed with 10% aqueous potassium carbonate (75 mL), followed by brine (50 mL) and (hied over sodium sulfate. The drying agent was removed by filtration, and the filtrate concentrated under reduced pressure to afford 5-methyl-2-nitro-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine in a 97% yield (5.70 g) as a yellow solid: 1H NMR (300 MHz, CDCl3) δ 6.62 (s, 1H), 4.28 (t, 2H, J=5.4 Hz), 3.67 (s, 2H), 2.95 (t, 2H, J=5.4 Hz), 2.52 (s, 3H); MS (EST+) m/z 183.0 (M+H).

1. customA 1-L Single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet
2. concentrationAfter this time the reaction was concentrated to dryness under reduced pressure
3. stirringthe resulting solid was stirred with a mixture of ethyl acetate (75 mL) and 10% aqueous potassium carbonate (75 mL)
4. customThe aqueous layer was separated
5. extractionextracted with ethyl acetate (2×75 mL)
6. washThe combined organic extracts were washed with 10% aqueous potassium carbonate (75 mL)
7. customThe drying agent was removed by filtration
8. concentrationthe filtrate concentrated under reduced pressure

ORD record

ord-1dd036aac7fd424c9e2f11e7903cf0bf

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08598174B2