1,3-Propanediol → 6-Fluoro-5-(3-hydroxy-propoxy)-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one

HRID 1633770노트

반응식

HRID 1633770 반응식
[F:1][C:2]1[C:3](/[C:12](/I)=[CH:13]/[C:14](=O)[C:15]2[NH:16][CH:17]=[CH:18][CH:19]=2)=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[CH2:5]2.[CH2:22]([OH:26])[CH2:23][CH2:24][OH:25].[H-].[Na+]>>[F:1][C:2]1[C:3]2[C:4]3[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]=3[C:14]([C:15]1[NH:16][CH:17]=[CH:18][CH:19]=1)=[CH:13][C:12]=2[O:25][CH2:24][CH2:23][CH2:22][OH:26]

참가 물질

4

반응물 3

HCID 104421,3-PropanediolHCID 24758Sodium hydrideHCID 10135347(Z)-5-fluoro-4-[1-iodo-3-oxo-3-(1H-pyrrol-2-yl)-propenyl]-1,3-dihydro-indol-2-one

생성물 1

HCID 98585056-Fluoro-5-(3-hydroxy-propoxy)-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one

실험 절차

To a suspension of (Z)-5-fluoro-4-[1-iodo-3-oxo-3-(1H-pyrrol-2-yl)-propenyl]-1,3-dihydro-indol-2-one (from Example 8 above) (198 mg, 0.5 mmol) in 1,3-propanediol (Fluka, 7.0 g, 92 mmol) was added NaH (Aldrich, 60%, 0.5 g, 12.5 mmol) in portions at room temperature. After stirring at room temperature for 30 minutes, the reaction mixture was heated to 110° C. for 2.5 hours. The reaction was quenched by pouring the reaction mixture into an ice-cold saturated aqueous ammonium chloride solution (50 mL) and extracted with ethyl acetate (3×50 mL). The combined organic extracts were successively washed with water (20 mL) and brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by flash chromatography (silica gel, 50% ethyl acetate in hexanes) to afford 6-fluoro-5-(3-hydroxy-propoxy)-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one as a yellow solid. (Yield 51.5 mg, 31.6%).

후처리

  1. temperaturethe reaction mixture was heated to 110° C. for 2.5 hours
  2. customThe reaction was quenched
  3. additionby pouring the reaction mixture into an ice-cold saturated aqueous ammonium chloride solution (50 mL)
  4. extractionextracted with ethyl acetate (3×50 mL)
  5. washThe combined organic extracts were successively washed with water (20 mL) and brine (20 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by flash chromatography (silica gel, 50% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-0f8e1e80a9c64196b9fc47e302806bf7
출처 데이터셋
uspto-grants-2003_01
특허 번호
US06504034B2

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