Sodium hydride → Ethyl 5-(cyclopropylmethyl)-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylate

HRID 2046205Notes

Reaction equation

HRID 2046205 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].Br[CH2:19][CH:20]1[CH2:22][CH2:21]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]([CH2:19][CH:20]3[CH2:22][CH2:21]3)[CH2:14][CH2:15][N:10]2[N:9]=1)=[O:7])[CH3:4]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 42873667Ethyl 4-oxo-4,5,6,7-tetrahydropyrazolo(1,5-a)pyrazine-2-carboxylate

Product 1

HCID 58465837Ethyl 5-(cyclopropylmethyl)-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylateYield 54%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A 60% dispersion of sodium hydride in mineral oils (0.11 g, 2.74 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 (0.48 g, 2.28 mmol) in DMF (11.4 mL) at 0° C. The mixture was stirred at room temperature for 15 minutes and then bromomethylcyclopropane (0.26 mL, 2.74 mmol) was added. The mixture was stirred at room temperature for 16 hours, diluted with water and extracted with AcOEt. 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 40/60). The desired fractions were collected and the solvents evaporated in vacuo to yield 5-cyclopropylmethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrazine-2-carboxylic acid ethyl ester (0.32 g, 54% yield) as a white solid.

Workup

  1. stirringThe mixture was stirred at room temperature for 16 hours
  2. extractionextracted with AcOEt
  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 40/60)
  9. customThe desired fractions were collected
  10. customthe solvents evaporated in vacuo

Sources & evidence

ORD record
ord-489246cdae734bb3b130925375f74b32
Source dataset
uspto-grants-2013_11
Patent number
US08592422B2

Reaction notes

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