Methyl iodide → 3-[4-(3,4-Dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-methyl-phenyl]-propionic Acid Tert-butyl Ester

HRID 220922Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 220922
[H-].[Na+].[C:3]([O:7][C:8](=[O:35])[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([N:19]2[CH2:28][C:27]3[CH:26]=[N:25][N:24]([CH3:29])[C:23]=3[NH:22][C:21]3[CH:30]=[CH:31][CH:32]=[CH:33][C:20]2=3)=[O:18])=[CH:13][C:12]=1[CH3:34])([CH3:6])([CH3:5])[CH3:4].CI.[CH3:38]COC(C)=O>CN(C=O)C>[C:3]([O:7][C:8](=[O:35])[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([N:19]2[CH2:28][C:27]3[CH:26]=[N:25][N:24]([CH3:29])[C:23]=3[N:22]([CH3:38])[C:21]3[CH:30]=[CH:31][CH:32]=[CH:33][C:20]2=3)=[O:18])=[CH:13][C:12]=1[CH3:34])([CH3:6])([CH3:5])[CH3:4]

Komponenten

6

Edukt 4

HCID 6328Methyl iodideHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 1361283503-[2-Methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenyl]-propionic Acid Tert-butyl Ester

Produkt 1

HCID 575552233-[4-(3,4-Dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-methyl-phenyl]-propionic Acid Tert-butyl EsterAusbeute 36 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

Sodium hydride (14 mg, 0.34 mmol) was added to a solution of 3-[2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenyl]-propionic acid tert-butyl ester from Example E45 (125 mg, 0.28 mmol) in DMF (2 ml) at 0° C. The mixture was stirred for 20 min at room temperature then cooled down to 0° C. Methyl iodide (0.09 ml, 1.4 mmol) was added and the mixture was stirred for 20 h at room temperature. EtOAc was added and the mixture was washed with 0.3M KHSO4 then brine, dried, concentrated in vacuo and azeotroped with toluene. The residue was purified by flash chromatography on silica gel through an isolute (eluant; EtOAc) to yield the title compound (46 mg, 36%).

Aufarbeitung

  1. temperaturethen cooled down to 0° C
  2. stirringthe mixture was stirred for 20 h at room temperature
  3. washthe mixture was washed with 0.3M KHSO4
  4. dry with materialbrine, dried
  5. concentrationconcentrated in vacuo
  6. customazeotroped with toluene
  7. customThe residue was purified by flash chromatography on silica gel through an isolute (eluant; EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-678dc428339148438f250f0ede335ec2
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08202858B2

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