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

HRID 1772094Notes

Reaction equation

HRID 1772094 reaction equation
Br[C:2]1[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=[C:6]([Br:8])[CH:7]=1.[CH3:11][N:12]1[C:16]([CH3:17])=[CH:15][C:14]([NH2:18])=[N:13]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:8][C:6]1[CH:7]=[C:2]([NH:18][C:14]2[CH:15]=[C:16]([CH3:17])[N:12]([CH3:11])[N:13]=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 70177471,5-dimethyl-1H-pyrazol-3-amine

Product 1

HCID 666135055-Bromo-3-(1,5-dimethyl-1H-pyrazol-3-ylamino)-1-methylpyridin-2(1H)-oneYield 56%

Reagents, catalysts & solvents 2

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

Procedure

A 250-mL single-necked round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 3,5-dibromo-1-methylpyridin-2(1H)-one (1.50 g, 5.62 mmol), 1,5-dimethyl-3-amino-1H-pyrazole (625 mg, 5.62 mmol), cesium carbonate (5.48 g, 16.8 mmol) and 1,4-dioxane (36 mL). After bubbling nitrogen through the resulting solution for 30 min, Xantphos (553 mg, 0.955 mmol) and tris(dibenzylideneacetone)dipalladium(0) (625 mg, 0.562 mmol) were added and the reaction mixture was heated at reflux for 16 h. The reaction mixture was cooled to room temperature and the resulting precipitate was filtered off. The filter cake was washed with methylene chloride (approximately 20 mL). The resulting filtrate was then concentrated under reduced pressure and purified by column chromatography to afford 105a (935 mg, 56%) as a yellow solid: 1H NMR (300 MHz, CDCl3) δ 7.84 (s, 1H), 7.31 (s, 1H), 6.86 (s, 1H), 5.65 (s, 1H), 3.71 (s, 3H), 3.57 (s, 3H), 2.23 (s, 3H); MS (ESI+) m/z 297.0 (M+H).

Workup

  1. customA 250-mL single-necked round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser
  3. customAfter bubbling nitrogen through the resulting solution for 30 min
  4. temperaturethe reaction mixture was heated
  5. temperatureat reflux for 16 h
  6. filtrationthe resulting precipitate was filtered off
  7. washThe filter cake was washed with methylene chloride (approximately 20 mL)
  8. concentrationThe resulting filtrate was then concentrated under reduced pressure
  9. custompurified by column chromatography

Sources & evidence

ORD record
ord-6fef535330014232a585a3c064c3d4e1
Source dataset
uspto-grants-2016_02
Patent number
US09249123B2

Reaction notes

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