Cesium carbonate → 5-Bromo-3-(5-ethyl-1H-pyrazol-3-ylamino)-1-methylpyridin-2(1H)-one

HRID 1918847Notes

Reaction equation

HRID 1918847 reaction equation
Br[C:2]1[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=[C:6]([Br:8])[CH:7]=1.[CH2:11]([C:13]1[NH:17][N:16]=[C:15]([NH2:18])[CH:14]=1)[CH3:12].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>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:8][C:6]1[CH:7]=[C:2]([NH:18][C:15]2[CH:14]=[C:13]([CH2:11][CH3:12])[NH:17][N:16]=2)[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-oneHCID 219910953-ethyl-1H-pyrazol-5-amine

Product 1

HCID 670161795-Bromo-3-(5-ethyl-1H-pyrazol-3-ylamino)-1-methylpyridin-2(1H)-oneYield 42.1%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
105 °C

Procedure

A 350-mL sealed tube equipped with a magnetic stirring bar was charged with 3,5-dibromo-1-methyl-1H-pyridin-2-one (3.2 g, 0.012 mol), 5-ethyl-1H-pyrazol-3-amine (2.0 g, 0.018 mol), Pd2(dba)3 (0.55 g, 0.60 mmol), 9,9-dimethyl-4,5-bis(diphenyl-phosphino)xanthene (0.49 g, 0.00084 mol), Cs2CO3 (7.8 g, 0.024 mol), and 1,4-dioxane (80 mL). After the reaction mixture was stirred at 105° C. for 16 h, it was cooled to room temperature, partitioned between dichloromethane (50 mL) and water (30 mL), and the organic phases were extracted with dichloromethane (30 mL×3). The combined organic phases were washed with water (30 mL×2) and brine (20 mL×1), dried (Na2SO4), and filtered through a pad of Celite, and the resulting filtrated was concentrated. To the crude product were added dichloromethane (20 mL) and ether (100 mL). The mixture was sonicated for 10 min., and the resulting precipitates were filtered to give 42% yield (1.5 g) of 5-bromo-3-(5-ethyl-1H-pyrazol-3-ylamino)-1-methylpyridin-2(1H)-one (125a) as a solid.

Workup

  1. customA 350-mL sealed tube
  2. customequipped with a magnetic stirring bar
  3. temperatureit was cooled to room temperature
  4. custompartitioned between dichloromethane (50 mL) and water (30 mL)
  5. extractionthe organic phases were extracted with dichloromethane (30 mL×3)
  6. washThe combined organic phases were washed with water (30 mL×2) and brine (20 mL×1)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered through a pad of Celite
  9. filtrationthe resulting filtrated
  10. concentrationwas concentrated
  11. additionTo the crude product were added dichloromethane (20 mL) and ether (100 mL)
  12. customThe mixture was sonicated for 10 min.
  13. customthe resulting precipitates
  14. filtrationwere filtered

Sources & evidence

ORD record
ord-39cdc33774f547e1830a229a427c9fa6
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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