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

HRID 425361
Notes
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Reaction equation

HRID 425361 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([C:11]2[N:12]([S:21]([N:24]([CH3:26])[CH3:25])(=[O:23])=[O:22])[CH:13]=[C:14]([CH2:16][C:17]([CH3:20])([CH3:19])[CH3:18])[N:15]=2)=[O:10])=[CH:4][CH:3]=1.CC(C)([O-])C.[Na+].[CH3:33][Si:34]([CH3:49])([CH3:48])[CH2:35][CH2:36][O:37][CH2:38][N:39]1[C:43]2[NH:44][CH2:45][CH2:46][CH2:47][C:42]=2[CH:41]=[N:40]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:18][C:17]([CH3:20])([CH3:19])[CH2:16][C:14]1[N:15]=[C:11]([C:9](=[O:10])[CH2:8][C:5]2[CH:6]=[CH:7][C:2]([N:44]3[CH2:45][CH2:46][CH2:47][C:42]4[CH:41]=[N:40][N:39]([CH2:38][O:37][CH2:36][CH2:35][Si:34]([CH3:49])([CH3:48])[CH3:33])[C:43]3=4)=[CH:3][CH:4]=2)[N:12]([S:21]([N:24]([CH3:26])[CH3:25])(=[O:23])=[O:22])[CH:13]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 27342162-(Dicyclohexylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 591403972-[(4-bromophenyl)acetyl]-4-(2,2-dimethylpropyl)-N,N-dimethyl-1H-imidazole-1-sulfonamide2×HCID 1360276751-{[2-(trimethylsilyl)ethoxy]methyl}-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 66705651
4-(2,2-dimethylpropyl)-N,N-dimethyl-2-{[4-(1-{[2-(trimethylsilyl)-ethoxy]methyl}-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-b]pyridin-7-yl)phenyl]acetyl}-1H-imidazole-1-sulfonamide

Reagents, catalysts & solvents 3

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

Conditions

Temperature
110 °C

Procedure

Palladium (II) acetate (13 mg, 0.06 mmol) was added to a degassed, ambient temperature solution of 2-[(4-bromophenyl)acetyl]-4-(2,2-dimethylpropyl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (Intermediate 7) (500 mg, 1.13 mmol), sodium tert-butoxide (436 mg, 4.52 mmol), 1-{[2-(trimethylsilyl)ethoxy]methyl}-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridine (574 mg, 2.26 mmol) and 2-(dicyclohexylphosphino)biphenyl (40 mg, 0.11 mmol) in 1,4-dioxane (10 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 0-60% ethyl acetate/hexane afforded 4-(2,2-dimethylpropyl)-N,N-dimethyl-2-{[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-b]pyridin-7-yl)phenyl]acetyl}-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-e603e63217ce434abb089f44a3a419a2
Source dataset
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08106070B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes