Cesium carbonate → N-[4-(4-fluoro-phenyl)-3-oxo-3,4-dihydro-pyrazin-2-yl]-2-phenoxy-acetamide

HRID 2046177Notes

Reaction equation

HRID 2046177 reaction equation
Cl[C:2]1[C:3](=[O:15])[N:4]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)[CH:5]=[CH:6][N:7]=1.[O:16]([CH2:23][C:24]([NH2:26])=[O:25])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(Cl)Cl>[F:14][C:11]1[CH:12]=[CH:13][C:8]([N:4]2[CH:5]=[CH:6][N:7]=[C:2]([NH:26][C:24](=[O:25])[CH2:23][O:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:3]2=[O:15])=[CH:9][CH:10]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 693142-PhenoxyacetamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 672214163-chloro-1-(4-fluorophenyl)pyrazin-2(1H)-one

Product 1

HCID 67974476N-[4-(4-fluoro-phenyl)-3-oxo-3,4-dihydro-pyrazin-2-yl]-2-phenoxy-acetamideYield 84%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Palladium (II) acetate (36 mg, 0.16 mmol) was added to a suspension of 3-chloro-1-(4-fluoro-phenyl)-1H-pyrazin-2-one (0.71 g, 3.2 mmol), phenoxyacetamide (0.57 g, 3.8 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.138 g, 0.24 mmol) and Cs2CO3 (1.5 g, 4.45 mmol) in 1,4-dioxane (10 mL). The mixture was stirred at 80° C. for 15 minutes. Then DCM was added, the solid was filtered off and washed with more DCM. The filtrate was separated and the solvent evaporated in vacuo and the crude product was purified by flash column chromatography (silica; AcOEt in DCM 1/99 to 1/4). The desired fractions were collected and the solvents evaporated in vacuo to yield N-[4-(4-fluoro-phenyl)-3-oxo-3,4-dihydro-pyrazin-2-yl]-2-phenoxy-acetamide (0.38 g, 84% yield).

Workup

  1. filtrationthe solid was filtered off
  2. washwashed with more DCM
  3. customThe filtrate was separated
  4. customthe solvent evaporated in vacuo
  5. customthe crude product was purified by flash column chromatography (silica; AcOEt in DCM 1/99 to 1/4)
  6. customThe desired fractions were collected
  7. customthe solvents evaporated in vacuo

Sources & evidence

ORD record
ord-2b8a5794456246c698f5bbba464fffb5
Source dataset
uspto-grants-2013_11
Patent number
US08592422B2

Reaction notes

Loading…