Cesium carbonate → 5-Bromo-1-methyl-3-(5-methyl-1H-pyrazol-3-ylamino)pyridin-2(1H)-one

HRID 1918818Notes

Reaction equation

HRID 1918818 reaction equation
[CH3:1][C:2]1[NH:6][N:5]=[C:4]([NH2:7])[CH:3]=1.Br[C:9]1[C:10](=[O:17])[N:11]([CH3:16])[CH:12]=[C:13]([Br:15])[CH:14]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Br:15][C:13]1[CH:14]=[C:9]([NH:7][C:4]2[CH:3]=[C:2]([CH3:1])[NH:6][N:5]=2)[C:10](=[O:17])[N:11]([CH3:16])[CH:12]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 931461H-Pyrazol-3-amine, 5-methyl-HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-one

Product 1

HCID 580441425-Bromo-1-methyl-3-(5-methyl-1H-pyrazol-3-ylamino)pyridin-2(1H)-oneYield 85%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
115 °C

Procedure

A 250 ml sealed tube with a magnetic stirrer was charged with 5-methyl-1H-pyrazol-3-amine (0.91 g, 9.36 mmol), 3,5-dibromo-1-methyl-1H-pyridin-2-one (2.1 g, 7.87 mmol), cesium carbonate (7.6 g, 23.56 mmol) and 1,4-dioxane (78 mL). After degassing for 10 minutes, tris(dibenzylideneacetone)dipalladium(0) (0.72 g, 0.8 mmol) and Xantphos (0.91 g, 1.57 mmol) were added. The reaction mixture was heated at 115° C. for 48 hours. Then the mixture was cooled to room temperature and partitioned between dichloro-methane (50 mL) and water (30 mL). The organic phase was separated, and the aqueous layer was extracted with dichloromethane (3×30 mL). The combined organic phases were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica, 9:1 methylene chloride/methanol) to give 85% yield (1.88 g) of 112a as a solid: MS (ESI+) m/z 285.0 (M+H).

Workup

  1. customA 250 ml sealed tube with a magnetic stirrer
  2. customAfter degassing for 10 minutes
  3. temperatureThen the mixture was cooled to room temperature
  4. custompartitioned between dichloro-methane (50 mL) and water (30 mL)
  5. customThe organic phase was separated
  6. extractionthe aqueous layer was extracted with dichloromethane (3×30 mL)
  7. dry with materialThe combined organic phases were dried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash column chromatography (silica, 9:1 methylene chloride/methanol)

Sources & evidence

ORD record
ord-2f111cdbedb3470bb8453c28341fcda8
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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