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Potassium Carbonate → (8R)-8-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-3-{1-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]cyclopropyl}-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine

HRID 1424124
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1424124
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]3[N:15]4[CH2:16][CH2:17][S:18][C@:19]([CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])([CH3:21])[CH2:20][C:14]4=[N:13][N:12]=3)[CH2:10][CH2:9]2)=[C:4]([F:31])[CH:3]=1.[CH3:32][N:33]1[CH:37]=[C:36](B2OC(C)(C)C(C)(C)O2)[CH:35]=[N:34]1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Si:24]([O:23][CH2:22][C@:19]1([CH3:21])[S:18][CH2:17][CH2:16][N:15]2[C:11]([C:8]3([C:5]4[CH:6]=[CH:7][C:2]([C:36]5[CH:35]=[N:34][N:33]([CH3:32])[CH:37]=5)=[CH:3][C:4]=4[F:31])[CH2:10][CH2:9]3)=[N:12][N:13]=[C:14]2[CH2:20]1)([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25]
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Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86712969(8R)-3-[1-(4-Bromo-2-fluorophenyl)cyclopropyl]-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine

Produkt 1

HCID 86712970(8R)-8-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-3-{1-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]cyclopropyl}-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine
Ausbeute 100,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel2×HCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

A solution of the compound (3.86 g, 7.32 mmol) obtained in Example 81-1), 1-methyl-1H-pyrazole-4-boronic acid pinacol ester (1.68 g, 8.06 mmol), tetrakis(triphenylphosphine)palladium(0) (850 mg, 0.73 mmol), and potassium carbonate (2.02 g, 14.65 mmol) in 1,2-dimethoxyethane (50 mL) and water (25 mL) was heated to reflux overnight with stirring. The reaction mixture was cooled to room temperature, water (20 mL) was added to the reaction mixture, the mixture was extracted with ethyl acetate, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After concentration under reduced pressure, the residue was purified by silica gel chromatography (ethyl acetate:methanol=100:0 to 70:30) to obtain the title compound (3.87 g, quant.) as a yellow solid.

Aufarbeitung

  1. temperatureto reflux overnight
  2. extractionthe mixture was extracted with ethyl acetate
  3. washthe organic layer was washed with saturated sodium chloride solution
  4. dry with materialdried with anhydrous sodium sulfate
  5. concentrationAfter concentration under reduced pressure
  6. customthe residue was purified by silica gel chromatography (ethyl acetate:methanol=100:0 to 70:30)

Quellen und Nachweise

ORD-Eintrag
ord-6d4999abbe4144689d9bf6c6bc4287a1
Quelldatensatz
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08927536B2

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