Isopropanol → 3-Bromo-1-ethyl-5-(pyrazin-2-yl)pyridin-2(1H)-one

HRID 1388665Notes

Reaction equation

HRID 1388665 reaction equation
C[O-].[Na+].[Br:4][C:5]1[C:6](=[O:17])[NH:7][CH:8]=[C:9]([C:11]2[CH:16]=[N:15][CH:14]=[CH:13][N:12]=2)[CH:10]=1.Br[CH2:19][CH3:20].C(O)(C)C>CN(C=O)C.C1(C)C=CC=CC=1>[Br:4][C:5]1[C:6](=[O:17])[N:7]([CH2:19][CH3:20])[CH:8]=[C:9]([C:11]2[CH:16]=[N:15][CH:14]=[CH:13][N:12]=2)[CH:10]=1

Participants

7

Reactant 4

HCID 3776IsopropanolHCID 6332Ethyl BromideHCID 10942334Sodium MethoxideHCID 136451023-Bromo-5-(pyrazin-2-yl)pyridin-2(1H)-one

Product 1

HCID 136451033-Bromo-1-ethyl-5-(pyrazin-2-yl)pyridin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

1.5 g of sodium methoxide is added to a stirred mixture of 3-bromo-5-(2-pyrazinyl)-2(1H)-pyridone (6.3 g) in DMF (200 ml) warmed to a temperature of 80° C. 4 ml of bromoethane are added to the warmed reaction mixture which is stirred for 30 minutes at 80° C. The reaction mixture is cooled to RT, stirred overnight, filtered and the filtrate acidified to pH 5.7 by addition of methanolic HCl. The acidified filtrate is evaporated resulting in a thick red oil. The oil is treated with hot isopropanol and the inorganic salts filtered off. The isopropanol solution is warmed, charcoal added, and filtered while hot. The filtrate is evaporated resulting in a tan solid which is dissolved in warm toluene and chromatographed on a column of silica gel (40 g per g tan solid) dispersed in toluene. The column is eluted increasing concentrations of ethyl acetate in toluene followed by methanol and ethyl acetate. The purified product is recrystallized from decane and toluene. The initial crop of crystals is identified as the O-ethylated product isomer while the addition of toluene caused the crystallization of a second crop of crystals which is identified as the desired N-ethyl pyridone, M.P. 129°-132° C.

Workup

  1. temperatureThe reaction mixture is cooled to RT
  2. stirringstirred overnight
  3. filtrationfiltered
  4. additionthe filtrate acidified to pH 5.7 by addition of methanolic HCl
  5. customThe acidified filtrate is evaporated
  6. customresulting in a thick red oil
  7. filtrationthe inorganic salts filtered off
  8. temperatureThe isopropanol solution is warmed
  9. additioncharcoal added
  10. filtrationfiltered while hot
  11. customThe filtrate is evaporated
  12. customresulting in a tan solid which
  13. customchromatographed on a column of silica gel (40 g per g tan solid)
  14. additiondispersed in toluene
  15. washThe column is eluted
  16. temperatureincreasing concentrations of ethyl acetate in toluene
  17. customThe purified product is recrystallized from decane and toluene
  18. additionThe initial crop of crystals is identified as the O-ethylated product isomer while the addition of toluene
  19. customthe crystallization of a second crop of crystals which

Sources & evidence

ORD record
ord-2e4a66115490403c967f1f2799dae721
Source dataset
uspto-grants-1984_02
Patent number
US04432979

Reaction notes

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