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

HRID 1913883ノート

反応式

HRID 1913883 の反応式
[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

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 83717Copper iodide触媒HCID 1140Toluene溶媒HCID 6212Chloroform溶媒

反応条件

温度
110 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-af0660fcba8a42d28cdfa8015bec2578
出典データセット
uspto-grants-2013_12
特許番号
US08609847B2

反応ノート

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