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 103i (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 dried 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 103j in a 97% yield (5.70 g) as a yellow solid: 1H NMR (300 MHz, CDCl3) d 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 (ESI+) 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. dry with materialdried over sodium sulfate
8. customThe drying agent was removed by filtration
9. concentrationthe filtrate concentrated under reduced pressure

ORD record

ord-a55a4060722a4e9294daa6c9d5be345f

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249123B2