Potassium Carbonate → HCID 57406361, compound

HRID 2202417Notes

Reaction equation

HRID 2202417 reaction equation
[C:1]([C:4]1[CH:9]=[C:8]([N:10]2[C:15]([CH3:16])=[CH:14][C:13]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:12]([Cl:27])[C:11]2=[O:28])[C:7]([CH3:29])=[CH:6][N:5]=1)(=O)[CH3:2].[C:30](OC(OC(C)(C)C)N(C)C)(C)(C)C.C(=O)([O-])[O-].[K+].[K+].Cl.[CH3:51][C:52]([CH3:57])([CH3:56])[C:53]([NH2:55])=[NH:54]>CN(C)C=O>[C:52]([C:53]1[N:55]=[C:1]([C:4]2[CH:9]=[C:8]([N:10]3[C:15]([CH3:16])=[CH:14][C:13]([O:17][CH2:18][C:19]4[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=4[F:26])=[C:12]([Cl:27])[C:11]3=[O:28])[C:7]([CH3:29])=[CH:6][N:5]=2)[CH:2]=[CH:30][N:54]=1)([CH3:57])([CH3:56])[CH3:51]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 5477121,1-bis(1,1-dimethylethoxy)-N,N,N-trimethylamineHCID 2781880Propanimidamide, 2,2-dimethyl-, hydrochloride (1:1)HCID 67777241HCID 67777241, compound

Product 1

HCID 57406361HCID 57406361, compoundYield 37.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2′-acetyl-3-chloro-4-[(2,4-difluorobenzyl)oxy]-5′,6-dimethyl-2H-1,4′-bipyridin-2-one (from step 7) (0.024 g, 0.057 mmol) in dimethylformamide (0.5 mL) was added N, N dimethylformamide di-tert-butyl acetal (0.02 g, 0.1 mmol) and heated at 60° C. for 2 h. The reaction mixture was concentrated in vacuo, the residue was dissolved in toluene (1 mL) and the solvent was removed in vacuo. The resulting residue was dried in vacuo for 2 h. It was dissolved in DMF (1 mL) and potassium carbonate (0.025 g, 0.18 mmol) and 2,2,2-trimethylacetamidine hydrochloride (0.02 g, 0.14 mmol) were added. This mixture was heated at 80 C. for 12 h under nitrogen. DMF was removed in vacuo and the residue was partitioned between water (5 mL) and ethyl acetate (15 mL). The organic phase was washed with water, dried with magnesium sulfate, and concentrated. The resulting residue was purified by silica-gel flash chromatography using 3% methanol in ethyl acetate. Appropriate fractions were combined and concentrated under reduced pressure to give 0.011 g of the title compound. ES-MS, m/z=511 (M+H).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionthe residue was dissolved in toluene (1 mL)
  3. customthe solvent was removed in vacuo
  4. customThe resulting residue was dried in vacuo for 2 h
  5. dissolutionIt was dissolved in DMF (1 mL)
  6. temperatureThis mixture was heated at 80 C
  7. customDMF was removed in vacuo
  8. customthe residue was partitioned between water (5 mL) and ethyl acetate (15 mL)
  9. washThe organic phase was washed with water
  10. dry with materialdried with magnesium sulfate
  11. concentrationconcentrated
  12. customThe resulting residue was purified by silica-gel flash chromatography
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5a35d9a6260448f3b79a75e9d751be21
Source dataset
uspto-grants-2016_06
Patent number
US09365546B2

Reaction notes

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