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 1881464ノート

反応式

HRID 1881464 の反応式
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

参加物

8

反応物 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

生成物 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

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
110 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-9548ae0f2c1a457e8009ae3b36b129fb
出典データセット
uspto-grants-2012_11
特許番号
US08318767B2

反応ノート

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