Potassium Carbonate → (2R)-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(1H-pyrazol-1-yl)phenyl]pyridin-1(2H)-yl}-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 84215Notes

Reaction equation

HRID 84215 reaction equation
C(=O)([O-])[O-].[K+].[K+].CC1(C)C(C)(C)OB([C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH:25]=[CH:24][CH:23]=[N:22]3)=[CH:17][CH:16]=2)O1.I[C:28]1[CH:33]=[CH:32][N:31]([CH2:34][CH2:35][C@@:36]([CH3:51])([S:47]([CH3:50])(=[O:49])=[O:48])[C:37]([NH:39][O:40][CH:41]2[CH2:46][CH2:45][CH2:44][CH2:43][O:42]2)=[O:38])[C:30](=[O:52])[CH:29]=1>COCCOC.CO.C(OCC)(=O)C>[CH3:51][C@@:36]([S:47]([CH3:50])(=[O:48])=[O:49])([CH2:35][CH2:34][N:31]1[CH:32]=[CH:33][C:28]([C:15]2[CH:16]=[CH:17][C:18]([N:21]3[CH:25]=[CH:24][CH:23]=[N:22]3)=[CH:19][CH:20]=2)=[CH:29][C:30]1=[O:52])[C:37]([NH:39][O:40][CH:41]1[CH2:46][CH2:45][CH2:44][CH2:43][O:42]1)=[O:38]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 57326595(2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideHCID 672491341-(4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrazole

Product 1

HCID 86671907(2R)-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(1H-pyrazol-1-yl)phenyl]pyridin-1(2H)-yl}-N-(tetrahydro-2H-pyran-2-yloxy)butanamideYield 23%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 86595564Dimethoxyethane methanolSolvent

Conditions

Temperature
80 °C

Procedure

Trisdibenzylidine dipalladium (29 mg, 0.049 mmol) was added to a mixture of potassium carbonate (343 mg, 2.46 mmol), 1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1H-pyrazole (133 mg, 0.49 mmol) and (2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (245 mg, 0.49 mmol), which may be synthesized as described in Preparation 2B in 1,2-dimethoxyethane-methanol (5.0 mL, 1:1). The reaction was heated to 80° C. and allowed to stir overnight. The reaction was diluted with ethyl acetate (10 mL), filtered through a pad of Celite, and concentrated under reduced pressure. The crude material was purified by flash chromatography (1:0-9:1 ethyl acetate/methanol) to provide a colorless residue (58 mg, 23%). MS (LCMS) m/z 513.7 (M−1).

Workup

  1. custommay be synthesized
  2. filtrationfiltered through a pad of Celite
  3. concentrationconcentrated under reduced pressure
  4. customThe crude material was purified by flash chromatography (1:0-9:1 ethyl acetate/methanol)

Sources & evidence

ORD record
ord-1c914165f7884d579e5c9776339f7925
Source dataset
uspto-grants-2014_09
Patent number
US08846933B2

Reaction notes

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