Salicylaldehyde oxime → 3-(1-Thiophen-2-yl-1H-pyrazol-5-yl)-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one

HRID 1407335

Reaktionsgleichung

Reaktionsgleichung von HRID 1407335
C(=NO)C1C(=CC=CC=1)O.C([O-])([O-])=O.[Cs+].[Cs+].[NH:17]1[C:21]([C:22]2[C:27](=[O:28])[CH:26]=[CH:25][N:24]([C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:37])[F:36])[CH:30]=3)[N:23]=2)=[CH:20][CH:19]=[N:18]1.I[C:40]1[S:41][CH:42]=[CH:43][CH:44]=1>CC#N.CCOC(C)=O.O.[Cu-]=O>[S:41]1[CH:42]=[CH:43][CH:44]=[C:40]1[N:17]1[C:21]([C:22]2[C:27](=[O:28])[CH:26]=[CH:25][N:24]([C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:37])([F:36])[F:38])[CH:30]=3)[N:23]=2)=[CH:20][CH:19]=[N:18]1

Komponenten

9

Edukt 4

HCID 7200Salicylaldehyde oximeHCID 10796Cesium carbonateHCID 189212-IodothiopheneHCID 594361503-(1H-pyrazol-5-yl)-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one

Produkt 1

HCID 580722563-(1-Thiophen-2-yl-1H-pyrazol-5-yl)-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-oneAusbeute 3 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178419072HCID 178419072, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To a mixture of copper (I) oxide (0.028 g, 0.20 mmol), salicylaldoxime (0.11 g, 0.78 mmol), Cs2CO3 (0.64 g, 2.0 mmol) and 3-(1H-pyrazol-5-yl)-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one (0.30 g, 0.98 mmol) in MeCN (8 mL) was added 2-iodothiophene (0.16 mL, 1.5 mmol), and the mixture was stirred at 90° C. for 1 day. The mixture was diluted with AcOEt and water, and filtered. The filtrate was partitioned between AcOEt and water. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was chromatographed on silica gel (20/80-100/0 AcOEt/hexane) to give yellow crystals. The crystals were purified by preparative HPLC and recrystallized from AcOEt/hexane to give the title compound (11 mg, 3% yield) as off-white crystals: NMR (300 MHz, CDCl3): δ ppm 6.75 (1H, d, J=7.9 Hz), 6.95 (1H, dd, J=5.5, 3.8 Hz), 7.01 (1H, dd, J=3.8, 1.3 Hz), 7.23 (1H, dd, J=5.5, 1.3 Hz), 7.31 (1H, d, J=8.7 Hz), 7.40 (1H, brs), 7.42 (1H, d, J=1.9 Hz), 7.51-7.57 (1H, m), 7.62 (1H, d, J=7.9 Hz), 7.81 (1H, d, J=1.9 Hz), 8.21 (1H, d, J=7.9 Hz). LC-MS (ESI) m/z 389 [M+H]+.

Aufarbeitung

  1. filtrationfiltered
  2. customThe filtrate was partitioned between AcOEt and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was chromatographed on silica gel (20/80-100/0 AcOEt/hexane)
  8. customto give yellow crystals
  9. customThe crystals were purified by preparative HPLC
  10. customrecrystallized from AcOEt/hexane

Quellen und Nachweise

ORD-Eintrag
ord-a63a88aef6014e289384d616e71ac751
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08916566B2

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