N,N'-Dimethylethylenediamine → 5-(4-Fluorophenyl)-4-oxo-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrazine-2-carboxylic acid ethyl ester

HRID 2046207Notes

Reaction equation

HRID 2046207 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:15]=[C:9]2[C:10](=[O:14])[NH:11][CH2:12][CH2:13][N:8]2[N:7]=1)=[O:5])[CH3:2].Br[C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1.CNCCNC.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.[Cu]I>[CH2:1]([O:3][C:4]([C:6]1[CH:15]=[C:9]2[C:10](=[O:14])[N:11]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[CH2:12][CH2:13][N:8]2[N:7]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 99931-Bromo-4-fluorobenzeneHCID 11430Potassium CarbonateHCID 42873667Ethyl 4-oxo-4,5,6,7-tetrahydropyrazolo(1,5-a)pyrazine-2-carboxylate

Product 1

HCID 679759865-(4-Fluorophenyl)-4-oxo-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrazine-2-carboxylic acid ethyl esterYield 90%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

Copper (I) iodide (0.18 g, 0.95 mmol) was added to a suspension of 4,5,6,7-tetrahydro-4-oxo-pyrazolo[1,5-a]pyrazine-2-carboxylic acid ethyl ester (1.0 g, 4.78 mmol), 1-bromo-4-fluorobenzene (1.0 mL, 9.56 mmol), N,N′-dimethylethylenediamine (0.30 mL, 2.86 mmol) and K2CO3 (1.3 g, 9.56 mmol) in toluene (20 mL). The reaction mixture was stirred at 130° C. for 16 hours. The mixture was filtered through a pad of diatomaceous earth which was washed with AcOEt. The mixture was diluted with AcOEt and washed with a 16% aqueous solution of NH4OH. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 30/70). The desired fractions were collected and the solvents evaporated in vacuo to yield 5-(4-fluorophenyl)-4-oxo-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrazine-2-carboxylic acid ethyl ester (1.3 g, 90% yield) as a white solid.

Workup

  1. filtrationThe mixture was filtered through a pad of diatomaceous earth which
  2. washwas washed with AcOEt
  3. additionThe mixture was diluted with AcOEt
  4. washwashed with a 16% aqueous solution of NH4OH
  5. customThe organic layer was separated
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customthe solvents evaporated in vacuo
  9. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 30/70)
  10. customThe desired fractions were collected
  11. customthe solvents evaporated in vacuo

Sources & evidence

ORD record
ord-de8c8cbf59b0468a8dc3a67b697914c7
Source dataset
uspto-grants-2013_11
Patent number
US08592422B2

Reaction notes

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