Water → 5-Bromo-3-(1,5-dimethyl-1H-pyrazol-3-ylamino)-1-methylpyridin-2(1H)-one

HRID 592900Notes

Reaction equation

HRID 592900 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:15]=[C:14]([CH3:16])[NH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[H-].[Na+].I[CH3:20].O>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:15]=[C:14]([CH3:16])[N:13]([CH3:20])[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 580441425-Bromo-1-methyl-3-(5-methyl-1H-pyrazol-3-ylamino)pyridin-2(1H)-one

Product 1

HCID 666135055-Bromo-3-(1,5-dimethyl-1H-pyrazol-3-ylamino)-1-methylpyridin-2(1H)-oneYield 33.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-bromo-1-methyl-3-(5-methyl-1H-pyrazol-3-ylamino)pyridin-2(1H)-one (2.8 g, 9.9 mmol) in anhydrous DMF (10 mL) was treated with 60% dispersion of NaH in mineral oil (0.51 g, 13 mmol) while stirring under nitrogen. After effervescence the reaction was stirred for an additional 30 minutes. At this time the reaction was treated with iodomethane (0.98 g, 7.0 mmol) with continued stirring under nitrogen for 2 hours. Water (50 mL) was added slowly and the mixture was filtered. The filtrate was extracted with ethyl acetate (3×30 mL). The combined extract was concentrated under reduced pressure and the residue was purified by flush column chromatography eluting with 3:1 petroleum ether/ethyl acetate to afford 218a (0.70 g, 24%). MS: [M+H]+ 297.

Workup

  1. stirringAfter effervescence the reaction was stirred for an additional 30 minutes
  2. stirringwith continued stirring under nitrogen for 2 hours
  3. filtrationthe mixture was filtered
  4. extractionThe filtrate was extracted with ethyl acetate (3×30 mL)
  5. extractionThe combined extract
  6. concentrationwas concentrated under reduced pressure
  7. customthe residue was purified
  8. customby flush column chromatography
  9. washeluting with 3:1 petroleum ether/ethyl acetate

Sources & evidence

ORD record
ord-fcf9b60a131f4b49bb92a839433fe117
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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