Benzyl Bromide → Ethyl 5-benzyl-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylate

HRID 2369579Notes

Reaction equation

HRID 2369579 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]([C:8]1[CH:17]=[C:11]2[C:12](=[O:16])[NH:13][CH2:14][CH2:15][N:10]2[N:9]=1)=[O:7])[CH3:4].[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C=O)C.O>[CH2:3]([O:5][C:6]([C:8]1[CH:17]=[C:11]2[C:12](=[O:16])[N:13]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:14][CH2:15][N:10]2[N:9]=1)=[O:7])[CH3:4]

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 42873667Ethyl 4-oxo-4,5,6,7-tetrahydropyrazolo(1,5-a)pyrazine-2-carboxylate

Product 1

HCID 58465696Ethyl 5-benzyl-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylateYield 83%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A 60% dispersion of sodium hydride in mineral oils (0.16 g, 4.0 mmol) was added to a stirred solution of 4,5,6,7-tetrahydro-4-oxo-pyrazolo[1,5-a]pyrazine-2-carboxylic acid ethyl ester (0.7 g, 3.35 mmol) in DMF (14 mL) at 0° C. The mixture was stirred at room temperature for 1 hour and then benzyl bromide (0.48 mL, 4.0 mmol) was added. The mixture was stirred at room temperature for 16 hours, diluted with H2O and extracted with DCM. The organic layer was separated, washed with brine, dried (NaSO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 50/50). The desired fractions were collected and the solvents evaporated in vacuo to yield 4,5,6,7-tetrahydro-4-oxo-5-(phenylmethyl)-pyrazolo[1,5-a]pyrazine-2-carboxylic acid ethyl ester (0.83 g, 83% yield) as a white oil. C16H17N3O3 LCMS: Rt 1.79, m/z 300 [M+H]+ (see LCMS Method 1).

Workup

  1. stirringThe mixture was stirred at room temperature for 16 hours
  2. extractionextracted with DCM
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried (NaSO4)
  6. filtrationfiltered
  7. customthe solvents evaporated in vacuo
  8. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 50/50)
  9. customThe desired fractions were collected
  10. customthe solvents evaporated in vacuo

Sources & evidence

ORD record
ord-459ab969ce14429cbbcf0e8eec81c8c2
Source dataset
uspto-grants-2014_04
Patent number
US08703946B2

Reaction notes

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