Cesium carbonate → Tert-butyl 4-(6-((5-bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-yl)amino)pyridin-3-yl)piperazine-1-carboxylate

HRID 1918958Notes

Reaction equation

HRID 1918958 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Br[C:22]1[C:23](=[O:30])[N:24]([CH3:29])[CH:25]=[C:26]([Br:28])[CH:27]=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:28][C:26]1[CH:27]=[C:22]([NH:1][C:2]2[N:7]=[CH:6][C:5]([N:8]3[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]3)=[CH:4][CH:3]=2)[C:23](=[O:30])[N:24]([CH3:29])[CH:25]=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 11737525tert-Butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate

Product 1

HCID 58043929Tert-butyl 4-(6-((5-bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-yl)amino)pyridin-3-yl)piperazine-1-carboxylateYield 59.6%

Reagents, catalysts & solvents 2

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

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 1,4-dioxane (50 mL), 188b (1.3 g, 4.7 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (1.24 g, 4.7 mmol), and cesium carbonate (3.8 g, 12 mmol). After bubbling nitrogen through the resulting mixture for 30 minutes, XantPhos (272 mg, 0.47 mmol) and tris(dibenzylideneacetone)dipalladium(0) (430 mg, 0.47 mmol) were added, and the reaction mixture was heated at reflux for 3 h. After this time the reaction was cooled to room temperature, partitioned between ethyl acetate (100 mL) and water (100 mL), and filtered. The aqueous layer was separated and extracted with ethyl acetate (50 mL×2). The organic layers were combined, washed with brine (50 mL), and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified on flash column eluting with 50:1 methylene chloride/methanol to afford 188c (1.3 g, 59%). MS: [M+H]+ 464.

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser
  3. customAfter bubbling nitrogen through the resulting mixture for 30 minutes
  4. temperaturethe reaction mixture was heated
  5. temperatureat reflux for 3 h
  6. custompartitioned between ethyl acetate (100 mL) and water (100 mL)
  7. filtrationfiltered
  8. customThe aqueous layer was separated
  9. extractionextracted with ethyl acetate (50 mL×2)
  10. washwashed with brine (50 mL)
  11. dry with materialdried over sodium sulfate
  12. customThe drying agent was removed by filtration
  13. concentrationthe filtrate was concentrated under reduced pressure
  14. customThe residue was purified on flash column
  15. washeluting with 50:1 methylene chloride/methanol

Sources & evidence

ORD record
ord-02bcb908b5c04b63b28e6b0cfa54beec
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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