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

HRID 84217Notes

Reaction equation

C(=O)([O-])[O-].[K+].[K+].[C:7]1(/[CH:13]=[CH:14]/B(O)O)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.I[C:19]1[CH:24]=[CH:23][N:22]([CH2:25][CH2:26][C@@:27]([CH3:42])([S:38]([CH3:41])(=[O:40])=[O:39])[C:28]([NH:30][O:31][CH:32]2[CH2:37][CH2:36][CH2:35][CH2:34][O:33]2)=[O:29])[C:21](=[O:43])[CH:20]=1.O1CCOCC1.O>C(OCC)(=O)C.[Pd]>[CH3:42][C@@:27]([S:38]([CH3:41])(=[O:39])=[O:40])([CH2:26][CH2:25][N:22]1[CH:23]=[CH:24][C:19](/[CH:14]=[CH:13]/[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[CH:20][C:21]1=[O:43])[C:28]([NH:30][O:31][CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][O:33]1)=[O:29]

Participants

Conditions

Temperature: 80 °C

Procedure

Pd EnCat™ (133 mg, 0.04 mmol, 0.1 equiv), was added to a mixture of potassium carbonate (166 mg, 1.2 mmol, 3.0 equiv), [(E)-2-phenylvinyl]boronic acid (65 mg, 0.44 mmol, 1.1 equiv), and (2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (200 mg, 0.40 mmol), which may be synthesized as described Preparation 2B, in 2:1 1,4-dioxane-water (3.6 mL). 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 ((1:1-0:1 heptane/ethyl acetate) to provide a white residue (90 mg, 47%). MS (LCMS) m/z 473.7 (M−1).

Workup

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

Sources & evidence

ORD record: ord-34730ec9012e4f77810bc95a4aa16bd5
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846933B2

Reaction notes

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