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 1625038노트

반응식

HRID 1625038 반응식
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

참가 물질

6

반응물 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

생성물 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

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 218864351,4-Dioxane--water (1/1)용매

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온도
80 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-1d55ed4f87fe4e2bb01a894b1afc2cde
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08779148B2

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