2-(Dicyclohexylphosphino)biphenyl → 4-(2,2-dimethylbutyl)-N,N-dimethyl-2-{1-(methylamino)-2-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-b]pyridin-7-yl)phenyl]ethyl}-1H-imidazole-1-sulfonamide

HRID 425383Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 425383
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([N:27]([CH3:38])C(=O)OCC2C=CC=CC=2)[C:10]2[N:11]([S:21]([N:24]([CH3:26])[CH3:25])(=[O:23])=[O:22])[CH:12]=[C:13]([CH2:15][C:16]([CH3:20])([CH3:19])[CH2:17][CH3:18])[N:14]=2)=[CH:4][CH:3]=1.CC(C)([O-])C.[Na+].[CH3:45][Si:46]([CH3:61])([CH3:60])[CH2:47][CH2:48][O:49][CH2:50][N:51]1[C:55]2[NH:56][CH2:57][CH2:58][CH2:59][C:54]=2[CH:53]=[N:52]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:19][C:16]([CH3:20])([CH2:17][CH3:18])[CH2:15][C:13]1[N:14]=[C:10]([CH:9]([NH:27][CH3:38])[CH2:8][C:5]2[CH:4]=[CH:3][C:2]([N:56]3[CH2:57][CH2:58][CH2:59][C:54]4[CH:53]=[N:52][N:51]([CH2:50][O:49][CH2:48][CH2:47][Si:46]([CH3:61])([CH3:60])[CH3:45])[C:55]3=4)=[CH:7][CH:6]=2)[N:11]([S:21]([N:24]([CH3:25])[CH3:26])(=[O:22])=[O:23])[CH:12]=1

Komponenten

8

Edukt 4

HCID 27342162-(Dicyclohexylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 86637799benzyl {2-(4-bromophenyl)-1-[1-[(dimethylamino)sulfonyl]-4-(2,2-dimethylbutyl)-1H-imidazol-2-yl]ethyl}methylcarbamateHCID 1360276751-{[2-(trimethylsilyl)ethoxy]methyl}-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridine

Produkt 1

HCID 667056104-(2,2-dimethylbutyl)-N,N-dimethyl-2-{1-(methylamino)-2-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-b]pyridin-7-yl)phenyl]ethyl}-1H-imidazole-1-sulfonamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

Palladium (II) acetate (5 mg, 0.02 mmol) was added to a degassed, ambient temperature solution of benzyl {2-(4-bromophenyl)-1-[1-[(dimethylamino)sulfonyl]-4-(2,2-dimethylbutyl)-1H-imidazol-2-yl]ethyl}methylcarbamate (267 mg, 0.44 mmol), sodium tert-butoxide (170 mg, 1.76 mmol), 1-{[2-(trimethylsilyl)ethoxy]methyl}-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridine (224 mg, 0.88 mmol) and 2-(dicyclohexylphosphino)biphenyl (15 mg, 0.04 mmol) in 1,4-dioxane (5 mL). After stirring at 110° C. overnight, the reaction mixture was cooled, diluted with water and extracted with methylene chloride and ethyl acetate. The combined organic extracts were dried (magnesium sulfate) and concentrated in vacuo. Chromatography over silica eluting with 0-100% acetone/methylene chloride afforded 4-(2,2-dimethylbutyl)-N,N-dimethyl-2-{1-(methylamino)-2-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-b]pyridin-7-yl)phenyl]ethyl}-1H-imidazole-1-sulfonamide.

Aufarbeitung

  1. temperaturethe reaction mixture was cooled
  2. extractionextracted with methylene chloride and ethyl acetate
  3. dry with materialThe combined organic extracts were dried (magnesium sulfate)
  4. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-bb1babf61ee444cda7d94a713514b735
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08106070B2

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