N,N'-Dimethylethylenediamine → 3-cyclohexyloxy-1-(4-fluoro-phenyl)-1H-pyrazin-2-one

HRID 2046175Notes

Reaction equation

HRID 2046175 reaction equation
[CH:1]1([O:7][C:8]2[C:9](=[O:14])[NH:10][CH:11]=[CH:12][N:13]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1.CNCCNC.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O1CCOCC1.[Cu]I>[CH:1]1([O:7][C:8]2[C:9](=[O:14])[N:10]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[CH:11]=[CH:12][N:13]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

8

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 99931-Bromo-4-fluorobenzeneHCID 62657Potassium Phosphate, TribasicHCID 575410493-(cyclohexyloxy)-2(1H)-pyrazinone

Product 1

HCID 679759613-cyclohexyloxy-1-(4-fluoro-phenyl)-1H-pyrazin-2-oneYield 76%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
180 °C

Procedure

Copper (I) iodide (0.98 g, 5.1 mmol) was added to a suspension of 3-(cyclohexyloxy)-2(1H)-pyrazinone (1.0 g, 5.1 mmol, prepared according to the method described in the Journal of Medicinal Chemistry, 52(7), 2076-2089; 2009), 1-bromo-4-fluorobenzene (0.85 mL, 7.7 mmol), N,N′-dimethylethylenediamine (0.55 mL, 5.1 mmol) and K3PO4 (2.18 g, 10.3 mmol) in a mixture of DMF (2 mL) and 1,4-dioxane (8 mL). The reaction mixture was stirred at 180° C. for 15 minutes under microwave irradiation. The solid was filtered off and washed with DCM, the filtrate was treated with a 32% solution of NH4OH. The organic layer was separated, dried (Na2SO4), filtered and the solvent evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 1/99 to 20/80). The desired fractions were collected and the solvents evaporated in vacuo to yield 3-cyclohexyloxy-1-(4-fluoro-phenyl)-1H-pyrazin-2-one (1.13 g, 76% yield).

Workup

  1. customprepared
  2. filtrationThe solid was filtered off
  3. washwashed with DCM
  4. additionthe filtrate was treated with a 32% solution of NH4OH
  5. customThe organic layer was separated
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customthe solvent evaporated in vacuo
  9. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 1/99 to 20/80)
  10. customThe desired fractions were collected
  11. customthe solvents evaporated in vacuo

Sources & evidence

ORD record
ord-b7f1237f31b34cd5a89caad43cce1c4b
Source dataset
uspto-grants-2013_11
Patent number
US08592422B2

Reaction notes

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