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Potassium Carbonate → {3-[1-(2-Fluorobiphenyl-4-yl)cyclopropyl]-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-8-yl}methanol

HRID 1424027
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1424027
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](C(C)(C)C)(C)C)([CH3:21])[CH2:20][C:14]4=[N:13][N:12]=3)[CH2:10][CH2:9]2)=[CH:4][C:3]=1[F:31].[C:32]1(B(O)O)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])O.[Na+]>C(COC)OC.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>[F:31][C:3]1[CH:4]=[C:5]([C:8]2([C:11]3[N:15]4[CH2:16][CH2:17][S:18][C:19]([CH2:22][OH:23])([CH3:21])[CH2:20][C:14]4=[N:13][N:12]=3)[CH2:9][CH2:10]2)[CH:6]=[CH:7][C:2]=1[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 4

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 516892Sodium BicarbonateHCID 867128783-[1-(4-Bromo-3-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 86712879
{3-[1-(2-Fluorobiphenyl-4-yl)cyclopropyl]-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-8-yl}methanol
Ausbeute 34 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

A solution of the compound (526 mg, 1.0 mmol) obtained in Example 25-3), phenylboronic acid (244 mg, 2.0 mmol), tetrakis(triphenylphosphine)palladium(0) (231 mg, 0.2 mmol), and potassium carbonate (276 mg, 2.0 mmol) in dimethoxyethane (4 mL) and water (1 mL) was stirred at 100° C. for 3.5 h. The reaction mixture was cooled to room temperature, saturated aqueous sodium hydrogencarbonate was added to the reaction mixture, the mixture was extracted with dichloromethane, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was partially purified by silica gel chromatography (Isco Combiflash, 40 g, methanol:ethyl acetate=0:100 to 40:60, gradient). A solution of this partially purified product and 4 M hydrochloric acid (1,4-dioxane solution, 2 mL) in methanol (2 mL) was stirred at room temperature for 14 h. The reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogencarbonate was added to the residue, the mixture was extracted with dichloromethane, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (Isco Combiflash, 12 g, methanol:ethyl acetate=0:100 to 40:60, gradient) to obtain the title compound (138 mg, 34%) as a colorless solid.

Aufarbeitung

  1. extractionthe mixture was extracted with dichloromethane
  2. washthe organic layer was washed with saturated sodium chloride solution
  3. dry with materialdried with anhydrous sodium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customthe residue was partially purified by silica gel chromatography (Isco Combiflash, 40 g, methanol:ethyl acetate=0:100 to 40:60, gradient)
  7. concentrationThe reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogencarbonate
  8. additionwas added to the residue
  9. extractionthe mixture was extracted with dichloromethane
  10. washthe organic layer was washed with saturated sodium chloride solution
  11. dry with materialdried with anhydrous sodium sulfate
  12. filtrationAfter filtration
  13. concentrationthe filtrate was concentrated under reduced pressure
  14. customthe residue was purified by silica gel chromatography (Isco Combiflash, 12 g, methanol:ethyl acetate=0:100 to 40:60, gradient)

Quellen und Nachweise

ORD-Eintrag
ord-930b0731e280477dad5644a95af898cd
Quelldatensatz
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08927536B2

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