Potassium Carbonate → HCID 44193639, compound

HRID 2079838Notes

Reaction equation

HRID 2079838 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:10][C:9]([CH3:12])([CH3:11])[C:8](=[O:13])[NH:7][C:6]=2[CH:14]=1.C([O-])(=O)C.[K+].Br[C:21]1[N:22]=[C:23]2[C:29]([C:30](=[O:35])[C:31]([CH3:34])([CH3:33])[CH3:32])=[CH:28][NH:27][C:24]2=[N:25][CH:26]=1.C(=O)([O-])[O-].[K+].[K+].C(=O)(O)[O-].[Na+]>O1CCOCC1.O.[Pd].[Cl-].[Cl-].C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Pd+2].C(OCC)(=O)C>[CH3:32][C:31]([CH3:34])([CH3:33])[C:30]([C:29]1[C:23]2[C:24](=[N:25][CH:26]=[C:21]([C:2]3[CH:3]=[CH:4][C:5]4[O:10][C:9]([CH3:12])([CH3:11])[C:8](=[O:13])[NH:7][C:6]=4[CH:14]=3)[N:22]=2)[NH:27][CH:28]=1)=[O:35]

Participants

11

Reactant 5

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 517044Potassium AcetateHCID 578292181-(2-Bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethylpropan-1-oneHCID 578292256-bromo-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one

Product 1

HCID 44193639HCID 44193639, compoundYield 35%

Reagents, catalysts & solvents 5

HCID 23938PalladiumCatalystHCID 178478645Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

Procedure

6-Bromo-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one (61 mg, 0.24 mmol, Bioorg. Med. Chem., 15 (2007), 5912) and bispinacolato diboron (73 mg, 0.29 mmol) were dissolved in 2.5 ml 1,4-dioxane. The solution and flask were purged with argon. Potassium acetate (59 mg, 0.6 mmol) and palladium bis(diphenylphosphino)ferrocene dichloride (10 mg, 0.012 mmol) were added and the sealed reaction was stirred at 100 C. for 3 hr. The reaction was cooled to room temperature and 1-(2-bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-propan-1-one (0.1 g, 0.35 mmol) was added. The reaction was diluted with 1 ml 1,4-dioxane and 0.6 ml water. Palladium bis(diphenylphosphino)ferrocene dichloride (15 mg, 0.019 mmol) and potassium carbonate (98 mg, 0.71 mmol) were added. The sealed vial was placed in a microwave reactor and run at 15° C. for 30 min. More palladium catalyst (7 mg, 0.0095 mmol) was added and the reaction repeated at 14° C. for 30 min. The reaction mixture was poured into ethyl acetate and sodium bicarbonate solution. The layers were separated and the aqueous layer was extracted once more with ethyl acetate. The combined ethyl acetate layers were washed with saturated sodium chloride solution and dried over sodium sulfate. After filtration and evaporation, the residue was purified by silica gel chromatography (methanol/dichloromethane) to give 31 mg (35%) of the product. MP=>300 C., (M+H)+=379.

Workup

  1. customThe solution and flask were purged with argon
  2. customthe sealed reaction
  3. customThe sealed vial was placed in a microwave reactor
  4. waitrun at 15° C. for 30 min
  5. waitthe reaction repeated at 14° C. for 30 min
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted once more with ethyl acetate
  8. washThe combined ethyl acetate layers were washed with saturated sodium chloride solution
  9. dry with materialdried over sodium sulfate
  10. filtrationAfter filtration and evaporation
  11. customthe residue was purified by silica gel chromatography (methanol/dichloromethane)

Sources & evidence

ORD record
ord-45a1f263ff844d5aaa72200f0538662d
Source dataset
uspto-grants-2011_04
Patent number
US07932254B2

Reaction notes

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