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 558220노트

반응식

HRID 558220 반응식
[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]

참가 물질

5

반응물 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

생성물 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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
-78 °C

실험 절차

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.

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-8dd33bcbf1904cae94ab53e457ee73c5
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08063049B2

반응 노트

불러오는 중…