Sodium hydride → alpha-[2-Chloro-4-(2,3,4,5-tetrahydro-5-methyl-3-oxo-1,2,4-triazin-6-yl)phenoxy]-N-[2-(3,4-dimethoxyphenyl)ethyl]acetamide

HRID 1198904Notes

Reaction equation

HRID 1198904 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]([CH3:16])[NH:11][C:12](=[O:15])[NH:13][N:14]=2)[CH:5]=[CH:6][C:7]=1[OH:8].[H-].[Na+].Cl[CH2:20][C:21]([NH:23][CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[C:28]([O:34][CH3:35])[CH:27]=1)=[O:22]>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]([CH3:16])[NH:11][C:12](=[O:15])[NH:13][N:14]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:20][C:21]([NH:23][CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[C:28]([O:34][CH3:35])[CH:27]=1)=[O:22]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 266222-Chloro-N-(2-(3,4-dimethoxy-phenyl)-ethyl)-acetamideHCID 1360298166-(3-Chloro-4-hydroxyphenyl)-4,5-dihydro-5-methyl-1,2,4-triazin-3(2H)-one

Product 1

HCID 14370693alpha-[2-Chloro-4-(2,3,4,5-tetrahydro-5-methyl-3-oxo-1,2,4-triazin-6-yl)phenoxy]-N-[2-(3,4-dimethoxyphenyl)ethyl]acetamideYield 38.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

442 mg of 6-(3-chloro-4-hydroxyphenyl)-4,5-dihydro-5-methyl-1,2,4-triazin-3(2H)-one [prepared as described in step (a) above] were added to a stirred suspension of 85 mg of sodium hydride (as a 55% w/w dispersion in mineral oil) in 7 ml of anhydrous dimethylformamide, whilst ice-cooling, and the mixture was stirred at room temperature for 1 hour. To the ice-cooled suspension were then added 472 mg of α-chloro-N-[2-(3,4-dimethoxyphenyl)ethyl]acetamide (prepared as described in Preparation 1), and the reaction mixture was stirred at room temperature for 1 hour and then at 100° C. (bath temperature) for a further 1 hour. The dimethylformamide used as the solvent was removed by evaporation under reduced pressure, and then the mixture was diluted with ethyl acetate. It was then washed with water and with a saturated aqueous solution of sodium chloride, dried and concentrated by evaporation under reduced pressure. The residue was collected by filtration and then recrystallized from a mixture of chloroform and ethyl acetate, to give 326 mg of the title compound as a white powder melting at 167°-169° C. (with decomposition).

Workup

  1. temperaturewhilst ice-cooling
  2. stirringthe reaction mixture was stirred at room temperature for 1 hour
  3. waitat 100° C. (bath temperature) for a further 1 hour
  4. customwas removed by evaporation under reduced pressure
  5. additionthe mixture was diluted with ethyl acetate
  6. washIt was then washed with water and with a saturated aqueous solution of sodium chloride
  7. customdried
  8. concentrationconcentrated by evaporation under reduced pressure
  9. filtrationThe residue was collected by filtration
  10. customrecrystallized from a mixture of chloroform and ethyl acetate

Sources & evidence

ORD record
ord-5abdf2c5388b4c23b2484d10303de7c2
Source dataset
uspto-grants-1990_02
Patent number
US04898862

Reaction notes

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