Potassium Carbonate → 7-(4-ethoxy-3-fluorophenyl)-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide

HRID 1978636Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1978636
Br[C:2]1[CH:3]=[CH:4][C:5]2[S:11](=[O:13])(=[O:12])[CH2:10][CH2:9][C:8]([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([CH2:23][N:24]([CH3:31])[CH:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[CH:19][CH:18]=3)=[O:15])=[CH:7][C:6]=2[CH:32]=1.B([O-])([O-])O[C:35]1[CH:40]=[CH:39][C:38]([O:41][CH2:42][CH3:43])=[C:37]([F:44])[CH:36]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.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>[CH2:42]([O:41][C:38]1[CH:39]=[CH:40][C:35]([C:2]2[CH:3]=[CH:4][C:5]3[S:11](=[O:13])(=[O:12])[CH2:10][CH2:9][C:8]([C:14]([NH:16][C:17]4[CH:18]=[CH:19][C:20]([CH2:23][N:24]([CH3:31])[CH:25]5[CH2:30][CH2:29][O:28][CH2:27][CH2:26]5)=[CH:21][CH:22]=4)=[O:15])=[CH:7][C:6]=3[CH:32]=2)=[CH:36][C:37]=1[F:44])[CH3:43]

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 219957067-bromo-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamideHCID 867567834-Ethoxy-3-fluorophenyl borate

Produkt 1

HCID 219958947-(4-ethoxy-3-fluorophenyl)-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamideAusbeute 41 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 86587398Ethanol toluene waterLösungsmittel

Versuchsvorschrift

Under argon atmosphere, a mixture of 7-bromo-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (300 mg), 4-ethoxy-3-fluorophenyl borate (117 mg) and potassium carbonate (160 mg) in toluene/ethanol/water (10/1/1 ml) was stirred at room temperature for 1 hour. To the mixture was added tetrakistriphenylphosphinepalladium (33 mg), and the mixture was refluxed for 24 hours, cooled, extracted with ethyl acetate, washed with saturated brine, dried with magnesium sulfate and concentrated under reduced pressure. The residue was purified with silica gel column chromatography (ethanol/ethyl acetate=1:4) to give crystals, which were recrystallized from ethanol to give pale yellow crystals of 7-(4-ethoxy-3-fluorophenyl)-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 50) (137 mg).

Aufarbeitung

  1. temperaturethe mixture was refluxed for 24 hours
  2. temperaturecooled
  3. extractionextracted with ethyl acetate
  4. washwashed with saturated brine
  5. dry with materialdried with magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified with silica gel column chromatography (ethanol/ethyl acetate=1:4)
  8. customto give crystals, which
  9. customwere recrystallized from ethanol

Quellen und Nachweise

ORD-Eintrag
ord-7cb2c4810a7b437482600e6b57225e1d
Quelldatensatz
uspto-grants-2001_05
Patentnummer
US06235771B1

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