Sodium hydride → N-(6-Cyano-9-thiazol-4-ylmethyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl)-isobutyramide

HRID 545537Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 545537
Cl.Cl[CH2:3][C:4]1[N:5]=[CH:6][S:7][CH:8]=1.C([O-])(O)=O.[Na+].[C:14]([C:16]1[CH:17]=[C:18]2[C:26](=[CH:27][CH:28]=1)[NH:25][C:24]1[CH2:23][CH2:22][CH:21]([NH:29][C:30](=[O:34])[CH:31]([CH3:33])[CH3:32])[CH2:20][C:19]2=1)#[N:15].[H-].[Na+]>CN(C=O)C.CCOC(C)=O.CCOCC>[C:14]([C:16]1[CH:17]=[C:18]2[C:26](=[CH:27][CH:28]=1)[N:25]([CH2:3][C:4]1[N:5]=[CH:6][S:7][CH:8]=1)[C:24]1[CH2:23][CH2:22][CH:21]([NH:29][C:30](=[O:34])[CH:31]([CH3:32])[CH3:33])[CH2:20][C:19]2=1)#[N:15]

Komponenten

8

Edukt 4

HCID 24758Sodium hydrideHCID 516892Sodium Bicarbonate2×HCID 27632894-(Chloromethyl)-1,3-thiazole hydrochlorideHCID 57431662N-(6-cyano-2,3,4,9-tetrahydro-1H-carbazol-3-yl)-isobutyramide

Produkt 1

HCID 59161218N-(6-Cyano-9-thiazol-4-ylmethyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl)-isobutyramideAusbeute 73,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 3283Diethyl EtherLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Partition 4-chloromethyl-thiazole hydrochloride (199 mg, 1.17 mmol) between Et2O (20 mL) and saturated aqueous NaHCO3 (20 mL). Separate the layers and dry the ether layer over MgSO4. Add DMF (3 mL) to the ether layer and concentrate in vacuo to remove the ether. Add this solution to a slurry of N-(6-cyano-2,3,4,9-tetrahydro-1H-carbazol-3-yl)-isobutyramide (Preparation 3) (300 mg, 1.07 mmol) and sodium hydride (60% suspension in mineral oil, 47 mg, 1.17 mmol) in DMF (3 mL) which has stirred for 30 min at room temperature. Stir the reaction at room temperature for 2 h, then add aqueous NaHCO3 (30 mL) and EtOAc (50 mL). Separate the layers and wash the organic portion with aqueous NaHCO3 (2×30 mL). Dry the organic layer (MgSO4). Filter and concentrate in vacuo to obtain 487 mg crude yellow solid. Recrystallize the material from boiling toluene (10 mL) to afford 296 mg (73%) of the title compound as a yellow solid. MS (ES): m/z 379 (M+1), 377 (M−1); 1H NMR (DMSO-d6): δ 9.01 (d, 1H, J=1.8 Hz), 7.90 (d, 1H, J=1.3 Hz), 7.84 (d, 1H, J=7.9 Hz), 7.69 (d, 1H, J=8.4 Hz), 7.56 (d, 1H, J=1.8 Hz), 7.40 (dd, 1H, J=8.6, 1.5 Hz), 5.47 (s, 2H), 3.99 (m, 1H), 3.03-2.81 (m, 3H), 2.49 (m, 1H), 2.37 (m, 1H), 1.98 (m, 1H), 1.80 (m, 1H), 0.99 (d, 6H, J=7.0 Hz); HPLC (Method A): Rt=1.93 min, (97%).

Aufarbeitung

  1. customSeparate the layers
  2. dry with materialdry the ether layer over MgSO4
  3. concentrationAdd DMF (3 mL) to the ether layer and concentrate in vacuo
  4. customto remove the ether
  5. stirringStir
  6. customthe reaction at room temperature for 2 h
  7. customSeparate the layers
  8. washwash the organic portion with aqueous NaHCO3 (2×30 mL)
  9. dry with materialDry the organic layer (MgSO4)
  10. filtrationFilter
  11. concentrationconcentrate in vacuo
  12. customto obtain 487 mg crude yellow solid
  13. customRecrystallize the material

Quellen und Nachweise

ORD-Eintrag
ord-4d85a41c112a43ae838e64b74186518c
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07935722B2

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