Dimethylformamide → 4-{5-[1-[4-(2,4-Bis-trifluoromethyl-benzyloxy)-3-methoxy-phenyl]-methylidene]-4-oxo-4,5-dihydro-thiazol-2-yl}-piperazine-1-carbothioic acid (4-methoxy-phenyl)-amide

HRID 1012204Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1012204
[F:1][C:2]([F:37])([F:36])[C:3]1[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][C:4]=1[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]=[C:14]2[S:18][C:17]([N:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)=[N:16][C:15]2=[O:25])=[CH:9][C:8]=1[O:26][CH3:27].CN(C=O)C.[O:43]([C:45]1[CH:50]=[CH:49][C:48]([N:51]=[C:52]=[S:53])=[CH:47][CH:46]=1)[CH3:44]>CC#N>[CH3:44][O:43][C:45]1[CH:50]=[CH:49][C:48]([NH:51][C:52]([N:22]2[CH2:21][CH2:20][N:19]([C:17]3[S:18][C:14](=[CH:13][C:10]4[CH:11]=[CH:12][C:7]([O:6][CH2:5][C:4]5[CH:28]=[CH:29][C:30]([C:32]([F:35])([F:33])[F:34])=[CH:31][C:3]=5[C:2]([F:36])([F:1])[F:37])=[C:8]([O:26][CH3:27])[CH:9]=4)[C:15](=[O:25])[N:16]=3)[CH2:24][CH2:23]2)=[S:53])=[CH:47][CH:46]=1

Komponenten

5

Edukt 3

HCID 6228DimethylformamideHCID 752934-Methoxyphenyl isothiocyanateHCID 73044183HCID 73044183, Verbindung

Produkt 1

HCID 730422054-{5-[1-[4-(2,4-Bis-trifluoromethyl-benzyloxy)-3-methoxy-phenyl]-methylidene]-4-oxo-4,5-dihydro-thiazol-2-yl}-piperazine-1-carbothioic acid (4-methoxy-phenyl)-amideAusbeute 15,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
55 °C

Versuchsvorschrift

To a N2 purged flask was added 5-[1-[4-(2,4-bis-trifluoromethyl-benzyloxy)-3-methoxy-phenyl]-methylidene]-2-piperazin-1-yl-thiazol-4-one (120 mg, 220 μmol) from Example 23, DMF (8 mL) and MeCN (8 mL). To the reaction solution was added 4-methoxylphenyl isothiocyanate (55 mg, 330 μmol). The reaction was stirred at 55° C. for 20 h and LC analysis should product was formed. The reaction solution was concentrated under reduced pressure and then taken into EtOAc (100 mL), washed with aq. NH4Cl (70 mL) and brine (50 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude material was chromatographed using reverse phase preparative HPLC, H2O/MeCN gradient 90:10 to 10:90) to provide the title compound as a white solid (24 mg, 13% yield). 1H NMR (DMSO-d6) δ 8.17 (1H, d, J=8.1 Hz), 8.11 (1H, s), 8.02 (1H, d, J=8.1 Hz), 7.64 (1H, s), 7.15-7.23 (5H, m), 6.88 (2H, d, J=8.9 Hz), 5.42 (2H, s), 4.16 (2H, br s), 4.09 (2H, m), 4.03 (2H, m), 3.86 (3H, s), 3.80 (2H, m), 3.74 (3H, s); MS (ESI) 711 (MH+).

Aufarbeitung

  1. customLC analysis should product was formed
  2. concentrationThe reaction solution was concentrated under reduced pressure
  3. washwashed with aq. NH4Cl (70 mL) and brine (50 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was chromatographed

Quellen und Nachweise

ORD-Eintrag
ord-b5a3251d973b4d2c98e044978de7df4b
Quelldatensatz
uspto-grants-2011_07
Patentnummer
US07977489B2

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