2-(Dicyclohexylphosphino)biphenyl → N-{1-[1-[(dimethylamino)sulfonyl]-4-(2,2-dimethylbutyl)-1H-imidazol-2-yl]-2-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-b]pyridin-7-yl)phenyl]ethyl}acetamide

HRID 1881486Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([NH:27][C:28](=[O:30])[CH3:29])[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+].[CH3:37][Si:38]([CH3:53])([CH3:52])[CH2:39][CH2:40][O:41][CH2:42][N:43]1[C:47]2[NH:48][CH2:49][CH2:50][CH2:51][C:46]=2[CH:45]=[N:44]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:25][N:24]([CH3:26])[S:21]([N:11]1[CH:12]=[C:13]([CH2:15][C:16]([CH3:20])([CH3:19])[CH2:17][CH3:18])[N:14]=[C:10]1[CH:9]([NH:27][C:28](=[O:30])[CH3:29])[CH2:8][C:5]1[CH:6]=[CH:7][C:2]([N:48]2[CH2:49][CH2:50][CH2:51][C:46]3[CH:45]=[N:44][N:43]([CH2:42][O:41][CH2:40][CH2:39][Si:38]([CH3:53])([CH3:52])[CH3:37])[C:47]2=3)=[CH:3][CH:4]=1)(=[O:23])=[O:22]

Participants

Conditions

Temperature: 110 °C

Procedure

Palladium (II) acetate (2 mg, 0.01 mmol) was added to a degassed, ambient temperature solution of N-{2-(4-bromophenyl)-1-[1-[(dimethylamino)sulfonyl]-4-(2,2-dimethylbutyl)-1H-imidazol-2-yl]ethyl}acetamide (100 mg, 0.2 mmol), sodium tert-butoxide (77 mg, 0.8 mmol), 1-{[2-(trimethylsilyl)ethoxy]methyl}-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridine (102 mg, 0.4 mmol) and 2-(dicyclohexylphosphino)biphenyl (7 mg, 0.02 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 0-60% acetone/methylene chloride afforded N-{1-[1-[(dimethylamino)sulfonyl]-4-(2,2-dimethylbutyl)-1H-imidazol-2-yl]-2-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-b]pyridin-7-yl)phenyl]ethyl}acetamide.

Workup

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

Sources & evidence

ORD record: ord-8240f48677f74bc5be7f5947dacaddd1
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08318767B2

Reaction notes

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