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

HRID 1913883Notes

Reaction equation

HRID 1913883 reaction equation
[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

Participants

8

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 1140TolueneSolventHCID 6212ChloroformSolvent

Conditions

Temperature
110 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-af0660fcba8a42d28cdfa8015bec2578
Source dataset
uspto-grants-2013_12
Patent number
US08609847B2

Reaction notes

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