Lithium Hexamethyldisilazide → 3-(1-(2-(Tert-butyldimethylsilyloxy)ethyl)cyclopropylsulfonyl)-8-chloro-1-(2-fluoro-4-iodophenyl)-5-methyl-3,4a,5,7a-tetrahydrodiimidazo[4,5-b:4',5'-e]pyridin-2(1H)-one

HRID 558220ノート

反応式

HRID 558220 の反応式
[Cl:1][C:2]1[C:7]2[N:8]=[CH:9][N:10]([CH3:11])[C:6]=2[N:5]=[C:4]2[NH:12][C:13](=[O:23])[N:14]([C:15]3[CH:20]=[CH:19][C:18]([I:21])=[CH:17][C:16]=3[F:22])[C:3]=12.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Si:34]([O:41][CH2:42][CH2:43][C:44]1([S:47](Cl)(=[O:49])=[O:48])[CH2:46][CH2:45]1)([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35]>C1COCC1>[Si:34]([O:41][CH2:42][CH2:43][C:44]1([S:47]([N:12]2[C:4]3=[N:5][CH:6]4[N:10]([CH3:11])[CH:9]=[N:8][CH:7]4[C:2]([Cl:1])=[C:3]3[N:14]([C:15]3[CH:20]=[CH:19][C:18]([I:21])=[CH:17][C:16]=3[F:22])[C:13]2=[O:23])(=[O:48])=[O:49])[CH2:46][CH2:45]1)([C:37]([CH3:39])([CH3:40])[CH3:38])([CH3:36])[CH3:35]

参加物

5

反応物 3

HCID 2733832Lithium HexamethyldisilazideHCID 593863261-[2-(Tert-butyldimethylsilanyloxy)ethyl]-cyclopropanesulfonyl chlorideHCID 595194258-Chloro-1-(2-fluoro-4-iodophenyl)-5-methyl-3,5-dihydrodiimidazo[4,5-b:4',5'-e]pyridin-2(1H)-one

生成物 1

HCID 669992833-(1-(2-(Tert-butyldimethylsilyloxy)ethyl)cyclopropylsulfonyl)-8-chloro-1-(2-fluoro-4-iodophenyl)-5-methyl-3,4a,5,7a-tetrahydrodiimidazo[4,5-b:4',5'-e]pyridin-2(1H)-one

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 8-chloro-1-(2-fluoro-4-iodophenyl)-5-methyl-3,5-dihydrodiimidazo[4,5-b:4′,5′-e]pyridin-2(1H)-one (example 16, step B) (150 mg, 0.35 mmol) in THF (5 ml) at −78° C. is added LiHMDS (0.39 ml, 1 M in THF, 0.39 mmol). The reaction mixture is stirred at −78° C. for 30 min and 1-(2-(tert-butyldimethylsilyloxy)ethyl)cyclopropane-1-sulfonyl chloride (144 mg, 0.48 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.

後処理

  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

出典と根拠

ORDレコード
ord-8dd33bcbf1904cae94ab53e457ee73c5
出典データセット
uspto-grants-2011_11
特許番号
US08063049B2

反応ノート

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