Sodium hydride → 2-(2,3-Dihydroxy-propylamino)-4-(6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-benzonitrile

HRID 1875409Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1875409
[CH3:1][C:2]1([CH3:16])[CH2:10][C:9]2[NH:8][N:7]=[C:6]([C:11]([F:14])([F:13])[F:12])[C:5]=2[C:4](=[O:15])[CH2:3]1.[H-].[Na+].[OH:19][CH:20]([CH2:32][OH:33])[CH2:21][NH:22][C:23]1[CH:30]=[C:29](F)[CH:28]=[CH:27][C:24]=1[C:25]#[N:26].[NH4+].[Cl-]>CC(N(C)C)=O>[OH:19][CH:20]([CH2:32][OH:33])[CH2:21][NH:22][C:23]1[CH:30]=[C:29]([N:8]2[C:9]3[CH2:10][C:2]([CH3:16])([CH3:1])[CH2:3][C:4](=[O:15])[C:5]=3[C:6]([C:11]([F:14])([F:13])[F:12])=[N:7]2)[CH:28]=[CH:27][C:24]=1[C:25]#[N:26]

Komponenten

6

Edukt 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 441904636,6-Dimethyl-3-(trifluoromethyl)-1,5,6,7-tetrahydro-4H-indazol-4-oneHCID 669527352-(2,3-Dihydroxy-propylamino)-4-fluorobenzonitrile

Produkt 1

HCID 669529362-(2,3-Dihydroxy-propylamino)-4-(6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-benzonitrileAusbeute 97,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

To a mixture of 6,6-Dimethyl-3-trifluoromethyl-1,5,6,7-tetrahydro-indazol-4-one (0.961 g, 4.14 mmol, 1 eq) and NaH (99 mg, 4.14 mmol, 1 eq) in dimethyl acetamide (20 mL) was added slowly 2-(2,3-Dihydroxy-propylamino)-4-fluoro-benzonitrile (0.87 g, 4.14 mmol, 1 eq). Then the reaction mixture was stirred at 150° C. overnight, cooled, poured into saturated NH4Cl aq. solution (100 mL), extracted by EtOAc (3×150 mL), dried over Na2SO4, filtered, concentrated. The crude product was purified by flash silica gel chromatography, eluted by EtOAc to give 2-(2,3-Dihydroxy-propylamino)-4-(6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-benzonitrile (1.7 g, 97% yield). LCMS (m/z): M+H=423.

Aufarbeitung

  1. temperaturecooled
  2. extractionextracted by EtOAc (3×150 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by flash silica gel chromatography
  7. washeluted by EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-640d19367093466cba1844c2dedd4039
Quelldatensatz
uspto-grants-2012_11
Patentnummer
US08309548B2

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