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 558220Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 558220
[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]

Komponenten

5

Edukt 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

Produkt 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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-8dd33bcbf1904cae94ab53e457ee73c5
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08063049B2

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