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

HRID 1161839노트

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HRID 1161839 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.[Si:35]([O:42][CH2:43][CH2:44][C:45]1([S:48](Cl)(=[O:50])=[O:49])[CH2:47][CH2:46]1)([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36]>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:48]([C:45]2([CH2:44][CH2:43][O:42][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])[CH2:46][CH2:47]2)(=[O:50])=[O:49])[C:10]1=[O:24]

참가 물질

5

반응물 3

HCID 2733832Lithium HexamethyldisilazideHCID 593863261-[2-(Tert-butyldimethylsilanyloxy)ethyl]-cyclopropanesulfonyl chlorideHCID 595194923-(2-Fluoro-4-iodophenyl)-4-fluoro-8-methyl-1H-imidazo[4,5-g]quinazolin-2(3H)-one

생성물 1

HCID 595194813-(2-Fluoro-4-iodophenyl)-1-(1-(2-(tert-butyldimethylsilyloxy)ethyl)cyclopropylsulfonyl)-4-fluoro-8-methyl-1H-imidazo[4,5-g]quinazolin-2(3H)-one

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 (example 34, step H) (90 mg, 0.22 mmol) in THF (5 ml) at −78° C. is added LiHMDS (0.29 ml, 1 M in THF, 0.29 mmol). The reaction mixture is stirred at −78° C. for 30 min and 1-(2-(tert-butyldimethylsilyloxy)ethyl)cyclopropane-1-sulfonyl chloride (99 mg, 0.33 mmol) is added to the mixture. The reaction is slowly warmed to room temperature and stirred at the temperature for 16 h. The reaction is quenched with saturated aqueous NH4Cl solution (20 ml) and extracted with EtOAc (2×30 ml). The combined organic solution is washed with brine (30 ml), dried over MgSO4 and concentrated. Silica gel chromatography yields the desired product.

후처리

  1. temperatureThe reaction is slowly warmed to room temperature
  2. stirringstirred at the temperature for 16 h
  3. customThe reaction is quenched with saturated aqueous NH4Cl solution (20 ml)
  4. extractionextracted with EtOAc (2×30 ml)
  5. washThe combined organic solution is washed with brine (30 ml)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated

출처 및 근거

ORD 기록
ord-85fd706a3867478ebedcc3c1496b513f
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07820664B2

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