Lithium Hexamethyldisilazide → 3-(2-Fluoro-4-iodophenyl)-1-(cyclopropylsulfonyl)-4-fluoro-8-methyl-1H-imidazo[4,5-g]quinazolin-2(3H)-one

HRID 558250노트

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HRID 558250 반응식
[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:21]2[C:12](=[CH:13][C:14]3[C:15]([CH3:23])=[N:16][CH:17]=[N:18][C:19]=3[C:20]=2[F:22])[NH:11][C:10]1=[O:24].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH:35]1([S:38](Cl)(=[O:40])=[O:39])[CH2:37][CH2:36]1>C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:21]2[C:12](=[CH:13][C:14]3[C:15]([CH3:23])=[N:16][CH:17]=[N:18][C:19]=3[C:20]=2[F:22])[N:11]([S:38]([CH:35]2[CH2:37][CH2:36]2)(=[O:40])=[O:39])[C:10]1=[O:24]

참가 물질

5

반응물 3

HCID 2733832Lithium HexamethyldisilazideHCID 2760919Cyclopropanesulfonyl chlorideHCID 595194923-(2-Fluoro-4-iodophenyl)-4-fluoro-8-methyl-1H-imidazo[4,5-g]quinazolin-2(3H)-one

생성물 1

HCID 595194453-(2-Fluoro-4-iodophenyl)-1-(cyclopropylsulfonyl)-4-fluoro-8-methyl-1H-imidazo[4,5-g]quinazolin-2(3H)-one수율 75%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
-78 °C

실험 절차

To a solution of 3-(2-fluoro-4-iodophenyl)-4-fluoro-8-methyl-1H-imidazo[4,5-g]quinazolin-2(3H)-one (50 mg, 0.12 mmol) in THF (10 ml) at −78° C. was added LiHMDS (0.16 ml, 1 M in THF, 0.16 mmol). The reaction mixture was stirred at −78° C. for 10 min and cyclopropylsulfonyl chloride (25 mg, 0.18 mmol) was added to the mixture. The reaction was slowly warmed to room temperature and stirred at the temperature for 16 h. The reaction was quenched with saturated aqueous NH4Cl solution (10 ml) and extracted with EtOAc (2×10 ml). The combined organic solution was washed with brine (20 ml), dried over MgSO4 and concentrated. Silica gel chromatography (EtOAc:Hexanes=25:75) yields 46 mg (75%) of the title compound as a yellow solid.

후처리

  1. temperatureThe reaction was slowly warmed to room temperature
  2. stirringstirred at the temperature for 16 h
  3. customThe reaction was quenched with saturated aqueous NH4Cl solution (10 ml)
  4. extractionextracted with EtOAc (2×10 ml)
  5. washThe combined organic solution was washed with brine (20 ml)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated

출처 및 근거

ORD 기록
ord-41fd616438fc46ddae9b93572df31e4f
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08063049B2

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