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 425383Notes

Reaction equation

HRID 425383 reaction equation
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

Participants

8

Reactant 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

Product 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

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-bb1babf61ee444cda7d94a713514b735
Source dataset
uspto-grants-2012_01
Patent number
US08106070B2

Reaction notes

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