Acetic Acid → HCID 178491035, Verbindung

HRID 460346

Reaktionsgleichung

Reaktionsgleichung von HRID 460346
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH2:7][CH2:8][C:9]2=O)=[CH:5][C:4]=1[O:13][CH2:14][CH2:15][CH2:16][O:17]C1CCCCO1.[CH3:24][O: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>O.C1COCC1>[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH2:7][C:8]3[C:9]2=[N:44][NH:45][C:33]=3[NH:32][C:28]2[CH:29]=[CH:30][CH:31]=[C:26]([O:25][CH3:24])[CH:27]=2)=[CH:5][C:4]=1[O:13][CH2:14][CH2:15][CH2:16][OH:17]

Komponenten

8

Edukt 5

HCID 176Acetic AcidHCID 9321HydrazineHCID 1378323-Methoxyphenyl isothiocyanate2×HCID 184458196-Methoxy-5-[3-(tetrahydro-pyran-2-yloxy)-propoxy]-indan-1-one2×HCID 57425481Lithium hexamethyldisilane

Produkt 1

HCID 178491035HCID 178491035, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A mixture of 6-methoxy-5-[3-(tetrahydro-pyran-2-yloxy)-propoxy]-indan-1-one (Intermediate L) (0.16 g, 0.0005 mole), 3-methoxy-phenyl isothiocyanate (Compound 19a) (0.08 mL, 0.0006 mole) and THF (1.5 mL) was added to lithium hexamethyldisilane (0.7 mL, 0.0007 mole) dropwise at room temperature with stirring. The reaction mixture was stirred for 4 hrs. Hydrazine (0.035 mL, 0.0011 mole) and acetic acid (0.66 mL, 0.0011 mole) were added to the reaction mixture, which was then heated at the reflux temperature for 18 hrs. To the resulting mixture was first added water (10 mL) and then the reaction mixture was extracted with CH2Cl2. The organic layers were combined and washed with aqueous NaHCO3 solution, then washed with water and brine solution, dried (Na2SO4), and solvent was removed in vacuo. The crude material was purified on the reverse phase HPLC and converted to the desired product upon standing in the 1% TFA in CH3CN: water solution. Lyophilization yielded the title compound, 3-[7-Methoxy-3-(3-methoxy-phenylamino)-2,4-dihydro-indeno[1,2-c]pyrazol-6-yloxy]-propan-1-ol as a white powder. MS m/z 382 (M+H)+; 1HNMR (DMSO-d6): 1.88(m, 2H), 3.40(s, 2H), 3.57(t, 2H), 3.72(s, 3H), 3.78(s, 3H), 4.05(t, 2H), 6.38(d, 1H), 6.68(d, 1H), 6.77(s, 1H), 7.10(m, 2H), 7.25(s, 1H), 8.75(br s, 1H).

Aufarbeitung

  1. stirringThe reaction mixture was stirred for 4 hrs
  2. temperaturewas then heated at the reflux temperature for 18 hrs
  3. extractionthe reaction mixture was extracted with CH2Cl2
  4. washwashed with aqueous NaHCO3 solution
  5. washwashed with water and brine solution
  6. dry with materialdried (Na2SO4), and solvent
  7. customwas removed in vacuo
  8. customThe crude material was purified on the reverse phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-dc44c90d68974025a9b5425256637827
Quelldatensatz
uspto-grants-2007_03
Patentnummer
US07196110B2

Verknüpfte Notizen

Wird geladen…