Potassium Carbonate → (2R)-4-[5-Fluoro-4-(3-fluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 1625038Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1625038
C(=O)([O-])[O-].[K+].[K+].[F:7][C:8]1[CH:9]=[C:10](B(O)O)[CH:11]=[CH:12][C:13]=1[O:14][CH3:15].[F:19][C:20]1[C:21](I)=[CH:22][C:23](=[O:44])[N:24]([CH2:26][CH2:27][C@@:28]([CH3:43])([S:39]([CH3:42])(=[O:41])=[O:40])[C:29]([NH:31][O:32][CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)=[O:30])[CH:25]=1>O1CCOCC1.O.[Pd]>[F:19][C:20]1[C:21]([C:10]2[CH:11]=[CH:12][C:13]([O:14][CH3:15])=[C:8]([F:7])[CH:9]=2)=[CH:22][C:23](=[O:44])[N:24]([CH2:26][CH2:27][C@@:28]([CH3:43])([S:39]([CH3:42])(=[O:40])=[O:41])[C:29]([NH:31][O:32][CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)=[O:30])[CH:25]=1

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 27821943-Fluoro-4-methoxyphenylboronic acidHCID 86670637(2R)-4-(5-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Produkt 1

HCID 86670650(2R)-4-[5-Fluoro-4-(3-fluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 23938PalladiumKatalysatorHCID 218864351,4-Dioxane--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Pd Encat™ (580 mg, 0.17 mmol) was added to a mixture of potassium carbonate (723 mg, 5.2 mmol), (3-fluoro-4-methoxyphenyl)boronic acid (318 mg, 2.1 mmol), and (2R)-4-(5-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide, T3, (900 mg, 1.7 mmol) in 1,4-dioxane:water (5:1, 24 mL). The reaction was heated to 80° C. and allowed to stir at this temperature overnight. The reaction was filtered through a pad of celite, which was washed with methanol (250 mL). The filtrate was concentrated under reduced pressure, and the resulting crude material was purified via flash chromatography using an eluent of EtOAc in heptanes (20-100%), then 10% methanol in EtOAc to provide the title compound as a light tan residue (800 mg, 99%). MS (LCMS) m/z 495.1 (M−1).

Aufarbeitung

  1. filtrationThe reaction was filtered through a pad of celite, which
  2. washwas washed with methanol (250 mL)
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customthe resulting crude material was purified via flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-1d55ed4f87fe4e2bb01a894b1afc2cde
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08779148B2

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