Dichloromethane → 3-[7-(2-Methoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-N,N-dimethyl-benzamide

HRID 1171133

Reaktionsgleichung

Reaktionsgleichung von HRID 1171133
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])=[CH:9][N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]2=[N:6][CH:7]=1.[CH3:29][N:30]([CH3:42])[C:31]([C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[CH:37][CH:38]=1)=[O:32].C(=O)(O)[O-].[Na+].ClCCl>C(#N)C.CCOC(C)=O.Cl[Pd-2](Cl)(P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CO>[CH3:18][O:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([C:37]3[CH:38]=[C:33]([CH:34]=[CH:35][CH:36]=3)[C:31]([N:30]([CH3:42])[CH3:29])=[O:32])[N:3]=2)[NH:8][CH:9]=1

Komponenten

9

Edukt 4

HCID 6344DichloromethaneHCID 516892Sodium Bicarbonate2×HCID 27733923-(Dimethylcarbamoyl)benzeneboronic acidHCID 598360452-Bromo-7-(2-methoxy-phenyl)-5-(toluene-4-sulfonyl)-5H-pyrrolo[2,3-b]pyrazine

Produkt 1

HCID 598361763-[7-(2-Methoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-N,N-dimethyl-benzamideAusbeute 54 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418903HCID 178418903, VerbindungKatalysatorHCID 887MethanolLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A mixture of 2-Bromo-7-(2-methoxy-phenyl)-5-(toluene-4-sulfonyl)-5H-pyrrolo[2,3-b]pyrazine (30 mg, 0.065 mmol), 3-dimethylaminocarbonylphenyl boronic acid (25.3 mg, 0.130 mmol) and dichlorobis(triphenylphosphino)palladium(II) (2.5 mg, 0.003 mmol) in acetonitrile (1 mL) and aqueous solution of sodium bicarbonate (2M, 1 mL) was irradiated in a Personal Chemistry Optimizer at 90° C. for 15 minutes. The crude reaction mixture was distributed between dichloromethane and a saturated aqueous solution of sodium bicarbonate. The aqueous phase was then extracted with dichloromethane and the combined organic phases were dried over sodium sulfate, filtered and concentrated. The crude brown residue was then dissolved in MeOH (5 mL), 5N KOH (50 μL) and the mixture was stirred at room temperature for 75 minutes. Removal of the solvents resulted in a yellow residue, which was then purified by flash silica gel chromatography using a gradient of ethyl acetate in hexanes, then 10% MeOH in EtOAc to afford 3-[7-(2-Methoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-N,N-dimethyl-benzamide (13.0 mg, 54% yield) as a pale yellow solid. 1H-NMR (500 MHz, CD3OD) δ 8.89 (m, 1H), 8.80 (m, 1H), 8.40 (m, 1H), 8.25 (m, 2H), 7.62 (m, 1H), 7.50 (m, 1H), 7.25 (m, 1H), 7.10 (m, 2H), 3.97 (m, 3H), 3.17 (m, 3H), 3.10 (m, 3H). MS: m/z 373.1 [MH+].

Aufarbeitung

  1. customwas irradiated in a Personal Chemistry Optimizer at 90° C. for 15 minutes
  2. customThe crude reaction mixture
  3. extractionThe aqueous phase was then extracted with dichloromethane
  4. dry with materialthe combined organic phases were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe crude brown residue was then dissolved in MeOH (5 mL)
  8. customRemoval of the solvents
  9. customresulted in a yellow residue, which
  10. customwas then purified by flash silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-f8c6b48a66624f6daaf0b16cb64e0ea5
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07829558B2

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