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 425383노트

반응식

HRID 425383 반응식
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

참가 물질

8

반응물 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

생성물 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

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
110 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-bb1babf61ee444cda7d94a713514b735
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08106070B2

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