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Acetic Acid → 3-[7-Ethoxy-3-(3-fluoro-phenylamino)-2,4-dihydro-indeno[1,2-c]pyrazol-6-yloxy]-propan-1-ol

HRID 460359
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 460359
[CH2:1]([O:3][C:4]1[CH:12]=[C:11]2[C:7]([CH2:8][CH2:9][C:10]2=O)=[CH:6][C:5]=1[O:14][CH2:15][CH2:16][CH2:17][O:18]C1CCCCO1)[CH3:2].[F:25][C:26]1[CH:27]=[C:28]([N:32]=[C:33]=S)[CH:29]=[CH:30][CH:31]=1.C[Si](C)(C)[Si](C)(C)C.[Li].[NH2:44][NH2:45].C(O)(=O)C>C(OCC)(=O)C.C1COCC1>[CH2:1]([O:3][C:4]1[CH:12]=[C:11]2[C:7]([CH2:8][C:9]3[C:10]2=[N:44][NH:45][C:33]=3[NH:32][C:28]2[CH:29]=[CH:30][CH:31]=[C:26]([F:25])[CH:27]=2)=[CH:6][C:5]=1[O:14][CH2:15][CH2:16][CH2:17][OH:18])[CH3:2]
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 5

HCID 176Acetic AcidHCID 9321HydrazineHCID 98343-Fluorophenyl isothiocyanate2×HCID 184458066-Ethoxy-5-[3-(tetrahydro-pyran-2-yloxy)-propoxy]-indan-1-oneHCID 57425481Lithium hexamethyldisilane

Produkt 1

HCID 178465802
3-[7-Ethoxy-3-(3-fluoro-phenylamino)-2,4-dihydro-indeno[1,2-c]pyrazol-6-yloxy]-propan-1-ol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a mixture of 6-Ethoxy-5-[3-(tetrahydro-pyran-2-yloxy)-propoxy]-indan-1-one (Intermediate AA) (0.100 g, 0.0003 mol), 3-fluorophenyl isothiocyanate (Compound 4a) (0.043 mL, 0.00036 mol) and THF (3 mL) was added lithium hexamethyldisilane (0.360 mL, 0.00036 mol) dropwise at room temperature with stirring. The reaction mixture was stirred for 48 h. Hydrazine (0.011 mL, 0.00036 mol) and acetic acid (0.021 mL, 0.00036 mol) was added to the reaction mixture, which was then heated at reflux temperature for 12 h. The reaction solution was then diluted with ethyl acetate, washed with water and dried over MgSO4. The solvent was removed in vacuo and the crude material was purified on the reverse phase HPLC and converted to the desired product upon standing in the 0.1% TFA solution. Lyophilization yielded the title compound as a white powder. MS m/z 384.2 (M+H)+;

Aufarbeitung

  1. stirringThe reaction mixture was stirred for 48 h
  2. temperaturewas then heated
  3. temperatureat reflux temperature for 12 h
  4. washwashed with water
  5. dry with materialdried over MgSO4
  6. customThe solvent was removed in vacuo
  7. customthe crude material was purified on the reverse phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-fc8a575e0cc74445b882d49375af1e7d
Quelldatensatz
uspto-grants-2007_03
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07196110B2

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