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

HRID 1913883노트

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HRID 1913883 반응식
[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

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 83717Copper iodide촉매HCID 1140Toluene용매HCID 6212Chloroform용매

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온도
110 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-af0660fcba8a42d28cdfa8015bec2578
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08609847B2

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