Dimethylformamide → 4-(4-(imidazo[1,2-b]pyridazin-6-ylmethoxy)phenyl)-5-(4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-one

HRID 1798697Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1798697
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9](=[O:23])[C:10]([CH3:22])([CH3:21])[O:11][C:12]=2[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C=O)C.Cl[CH2:36][C:37]1[CH:38]=[CH:39][C:40]2[N:41]([CH:43]=[CH:44][N:45]=2)[N:42]=1>O>[N:45]1[CH:44]=[CH:43][N:41]2[C:40]=1[CH:39]=[CH:38][C:37]([CH2:36][O:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]3[C:9](=[O:23])[C:10]([CH3:21])([CH3:22])[O:11][C:12]=3[C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)=[CH:6][CH:7]=1)=[N:42]2

Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 595801634-(4-hydroxyphenyl)-5-(4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-oneHCID 595801656-(Chloromethyl)imidazo[1,2-b]pyridazine

Produkt 1

HCID 497789784-(4-(imidazo[1,2-b]pyridazin-6-ylmethoxy)phenyl)-5-(4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-oneAusbeute 47,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

4-(4-Hydroxyphenyl)-5-(4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-one (1.2 g, 3.8 mmol) was added to a mixture of cesium carbonate (3.7 g, 11.6 mmol) and DMF (25 mL) at RT under an atmosphere of nitrogen. The reaction mixture was stirred at RT for 30 min upon which 6-(chloromethyl) imidazo[1,2-b]pyridazine (0.96 g, 5 mmol) was added. The mixture was heated at 80° C. for 4 h (the reaction was monitored by TLC). The reaction mixture was diluted with water and extracted with EtOAc. The combined organics were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography using 30% ethyl acetate in n-hexane and silica gel (230-400 mesh) to afford 4-(4-(imidazo[1,2-b]pyridazin-6-ylmethoxy)phenyl)-5-(4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-one (0.8 g, 47%) as Off-white solid. 1H NMR: 200 MHz, DMSO-d6: δ 8.35 (s, 1H), 8.2 (d, 1H), 7.8 (s, 1H), 7.55 (d, 2H), 7.4 (d, 1H), 7.2 (d, 2H), 7.1 (d, 2H), 7.0 (d, 2H), 5.3 (s, 2H), 3.9 (s, 3H), 1.45 (s, 6H). MS: [M+H]+: m/z=442.1. HPLC: (95.8%, Condition-A).

Aufarbeitung

  1. additionwas added
  2. extractionextracted with EtOAc
  3. dry with materialThe combined organics were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-c21a1873fbbb47159aeaa9241c38cb76
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08343973B2

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