Sodium hydride → [2-[6-fluoro-2-oxo-3-(1H-pyrrol-2-yl)-1,2-dihydro-benzo[cd]indol-5-yloxy]-ethyl]-carbamic acid tert-butyl ester

HRID 1633771노트

반응식

HRID 1633771 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.[OH:22][CH2:23][CH2:24][NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29].[H-].[Na+]>>[C:28]([O:27][C:26](=[O:32])[NH:25][CH2:24][CH2:23][O:22][C:12]1[CH:13]=[C:14]([C:15]2[NH:16][CH:17]=[CH:18][CH:19]=2)[C:5]2[C:6](=[O:11])[NH:7][C:8]3[C:4]=2[C:3]=1[C:2]([F:1])=[CH:10][CH:9]=3)([CH3:31])([CH3:29])[CH3:30]

참가 물질

4

반응물 3

HCID 24758Sodium hydrideHCID 2733206tert-butyl N-(2-hydroxyethyl)carbamateHCID 10135347(Z)-5-fluoro-4-[1-iodo-3-oxo-3-(1H-pyrrol-2-yl)-propenyl]-1,3-dihydro-indol-2-one

생성물 1

HCID 23550271[2-[6-fluoro-2-oxo-3-(1H-pyrrol-2-yl)-1,2-dihydro-benzo[cd]indol-5-yloxy]-ethyl]-carbamic acid tert-butyl ester

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) (79.2 mg, 0.2 mmol) in tert-butyl N-(2-hydroxyethyl)-carbamate (Aldrich, 3 mL, 18.9 mmol) was added NaH (Aldrich, 60%, 0.2 g, 5.0 mmol) in portions at room temperature. After stirring at room temperature for 30 minutes, the reaction mixture was heated to 120° C. for 3.0 hours. The reaction was quenched by pouring the reaction mixture into an ice-cold saturated aqueous ammonium chloride solution (20 mL) and extracted with ethyl acetate (3×30 mL). The combined organic extracts were successively washed with water (10 mL) and brine (10 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 give [2-[6-fluoro-2-oxo-3-(1H-pyrrol-2-yl)-1,2-dihydro-benzo[cd]indol-5-yloxy]-ethyl]-carbamic acid tert-butyl ester as a yellow solid. (Yield 17.7 mg, 21.5%).

후처리

  1. temperaturethe reaction mixture was heated to 120° C. for 3.0 hours
  2. customThe reaction was quenched
  3. additionby pouring the reaction mixture into an ice-cold saturated aqueous ammonium chloride solution (20 mL)
  4. extractionextracted with ethyl acetate (3×30 mL)
  5. washThe combined organic extracts were successively washed with water (10 mL) and brine (10 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-2d8e5b6b3ccf487782d091bcb891d83a
출처 데이터셋
uspto-grants-2003_01
특허 번호
US06504034B2

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