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

HRID 1919104Notes

Reaction equation

HRID 1919104 reaction equation
[CH2:1]([N:3]1[C:7]([CH3:8])=[CH:6][C:5]([NH2:9])=[N:4]1)[CH3:2].Br[C:11]1[C:12](=[O:19])[N:13]([CH3:18])[CH:14]=[C:15]([Br:17])[CH:16]=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>O1CCOCC1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(OCC)(=O)C.O>[Br:17][C:15]1[CH:16]=[C:11]([NH:9][C:5]2[CH:6]=[C:7]([CH3:8])[N:3]([CH2:1][CH3:2])[N:4]=2)[C:12](=[O:19])[N:13]([CH3:18])[CH:14]=1

Participants

9

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 64853841-ethyl-5-methyl-1H-pyrazol-3-amine

Product 1

HCID 580442355-Bromo-3-(1-ethyl-5-methyl-1H-pyrazol-3-ylamino)-1-methylpyridin-2(1H)-oneYield 40%

Reagents, catalysts & solvents 4

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A sealed tube was equipped with a magnetic stirrer and charged with 1-ethyl-5-methyl-1H-pyrazol-3-amine (870 mg, 7 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (1.9 g, 7 mmol) and cesium carbonate (5 g, 15 mmol) in 1,4-dioxane (69 mL). After bubbling nitrogen through the solution for 30 min, Xantphos (480 mg, 0.8 mmol) and tris(dibenzylideneacetone) dipalladium(0) (450 mg, 0.5 mmol) were added, and the reaction mixture was heated to 100° C. for 16 h. After this time, water (50 mL) and ethyl acetate (50 mL) were added. The aqueous layer was separated and extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with brine (100 mL) and dried over sodium sulfate. The mixture was concentrated under reduced pressure to near dryness when the desired product crashed out and was filtered. Washing with diethyl ether (10 mL) afforded a 40% yield (870 mg) of 302a.

Workup

  1. customA sealed tube was equipped with a magnetic stirrer
  2. customAfter bubbling nitrogen through the solution for 30 min
  3. customThe aqueous layer was separated
  4. extractionextracted with ethyl acetate (2×50 mL)
  5. washThe combined organic extracts were washed with brine (100 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationThe mixture was concentrated under reduced pressure
  8. filtrationwas filtered
  9. washWashing with diethyl ether (10 mL)

Sources & evidence

ORD record
ord-7cec2f8727e9478a9b3e99185f5b18ac
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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