Cesium carbonate → 6-[(1-cyclobutylpiperidin-4-yl)oxy]-3,4-dihydro-2H-1,3'-biquinolin-2-one

HRID 1913883Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1913883
[CH:1]1([N:5]2[CH2:10][CH2:9][CH:8]([O:11][C:12]3[CH:13]=[C:14]4[C:19](=[CH:20][CH:21]=3)[NH:18][C:17](=[O:22])[CH2:16][CH2:15]4)[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.Br[C:24]1[N:25]=[CH:26][C:27]2[C:32]([CH:33]=1)=[CH:31][CH:30]=[CH:29][CH:28]=2.CN[C@@H]1CCCC[C@H]1NC.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl.[Cu](I)I>[CH:1]1([N:5]2[CH2:6][CH2:7][CH:8]([O:11][C:12]3[CH:13]=[C:14]4[C:19](=[CH:20][CH:21]=3)[N:18]([C:27]3[CH:26]=[N:25][C:24]5[C:29]([CH:28]=3)=[CH:30][CH:31]=[CH:32][CH:33]=5)[C:17](=[O:22])[CH2:16][CH2:15]4)[CH2:9][CH2:10]2)[CH2:4][CH2:3][CH2:2]1

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 6409693-BromoisoquinolineHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 666826006-(1-cyclobutylpiperidin-4-yloxy)-3,4-dihydroquinolin-2(1H)-one

Produkt 1

HCID 468662216-[(1-cyclobutylpiperidin-4-yl)oxy]-3,4-dihydro-2H-1,3'-biquinolin-2-oneAusbeute 44 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 83717Copper iodideKatalysatorHCID 1140TolueneLösungsmittelHCID 6212ChloroformLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A suspension of 6-(1-cyclobutylpiperidin-4-yloxy)-3,4-dihydroquinolin-2(1H)-one synthesized in Example 4-(1) (0.10 g), 3-bromoisoquinoline (0.10 g), rac-trans-N,N′-dimethylcyclohexane-1,2-diamine (0.047 g), copper iodide (0.016 g) and cesium carbonate (0.22 g) in toluene (1 mL) was stirred at 110° C. for 3 hours. The reaction mixture was cooled to room temperature, diluted with chloroform and filtered to remove insoluble materials. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by NH-type silica gel column chromatography (eluting solvent: hexane/ethyl acetate=4/1 to 1/4) and OH-type preparative TLC (on two plates of 1 mm thickness, developing solvent: chloroform/methanol=4/1) to give the titled compound (0.061 g, 44%) as a colorless amorphous substance.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. customto remove insoluble materials
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customthe resulting residue was purified by NH-type silica gel column chromatography (eluting solvent: hexane/ethyl acetate=4/1 to 1/4) and OH-type preparative TLC (on two plates of 1 mm thickness, developing solvent: chloroform/methanol=4/1)

Quellen und Nachweise

ORD-Eintrag
ord-af0660fcba8a42d28cdfa8015bec2578
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08609847B2

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