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

HRID 1161837ノート

反応式

HRID 1161837 の反応式
[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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-da177f97aeb74a22a767056963d8ef9d
出典データセット
uspto-grants-2010_10
特許番号
US07820664B2

反応ノート

読み込み中…