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

HRID 872141Notes

Reaction equation

HRID 872141 reaction equation
Br[CH2:2][CH2:3][N:4]1[C:8]([CH2:9]O)=[CH:7][C:6]([N+:11]([O-:13])=[O:12])=[N:5]1.[CH3:14][NH2:15]>C1COCC1>[CH3:14][N:15]1[CH2:2][CH2:3][N:4]2[N:5]=[C:6]([N+:11]([O-:13])=[O:12])[CH:7]=[C:8]2[CH2:9]1

Participants

4

Reactant 2

HCID 6329MethylamineHCID 58043832(1-(2-bromoethyl)-3-nitro-1H-pyrazol-5-yl)methanol

Product 1

HCID 580440245-Methyl-2-nitro-4,5,6,7-tetrahydropyrazolo[1,5-A]pyrazineYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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 101j (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 101k 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).

Workup

  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

Sources & evidence

ORD record
ord-31e6af630c2249f3b8792410e2f61a84
Source dataset
uspto-grants-2015_03
Patent number
US08975260B2

Reaction notes

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