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

HRID 1185076Notes

Reaction equation

HRID 1185076 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 35.3%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 1,4-dioxane (15 mL), 5-methyl-1H-pyrazol-3-amine (1 g, 10 mmol) (1), 3,5-dibromo-1-methylpyridin-2(1H)-one (4 g, 15 mmol) (2), and cesium carbonate (6.4 g, 20 mmol). Xantphos (400 mg, 0.8 mmol) and Pd2(dba)3 (700 mg, 0.8 mmol) were added, and the reaction mixture was heated at 100° C. for 5 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified on flush column eluting with dichloromethane:methanol (20:1) to afford 118a (1.0 g, 35%). MS: [M+H]+ 283.

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser
  3. temperatureAfter this time the reaction was cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified
  7. customon flush column
  8. washeluting with dichloromethane:methanol (20:1)

Sources & evidence

ORD record
ord-9d73f9830dc0415ca9c10840a054d367
Source dataset
uspto-grants-2014_03
Patent number
US08669251B2

Reaction notes

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