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1,4-Dioxane → (S)-1-(3-(4,6-dimethylquinolin-2-ylamino)pyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone

HRID 1666619
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HRID 1666619 반응식
Cl[C:2]1[CH:11]=[C:10]([CH3:12])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH3:13])[CH:8]=2)[N:3]=1.Cl.[NH2:15][C@H:16]1[CH2:20][CH2:19][N:18]([C:21](=[O:34])[CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][C:30]([F:33])([F:32])[F:31])=[CH:25][CH:24]=2)[CH2:17]1.O1CCOCC1.CC(C)([O-])C.[Na+]>C(OCC)(=O)C.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:12][C:10]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH3:13])[CH:8]=2)[N:3]=[C:2]([NH:15][C@H:16]2[CH2:20][CH2:19][N:18]([C:21](=[O:34])[CH2:22][C:23]3[CH:24]=[CH:25][C:26]([O:29][C:30]([F:31])([F:32])[F:33])=[CH:27][CH:28]=3)[CH2:17]2)[CH:11]=1
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참가 물질

8

반응물 4

HCID 312751,4-DioxaneHCID 6057692-Chloro-4,6-dimethylquinolineHCID 23676156Sodium t-butoxideHCID 86636479(S)-1-(3-aminopyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone mono hydrochloride

생성물 1

HCID 57970107(S)-1-(3-(4,6-dimethylquinolin-2-ylamino)pyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone수율 64.8%

시약·촉매·용매

3
HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 8857Ethyl Acetate용매

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온도
70 °C

실험 절차

To a mixture of 2-chloro-4,6-dimethylquinoline (0.20 g), Pd2(dba)3 (0.048 g), (±)-BINAP (0.10 g), (S)-1-(3-aminopyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone mono hydrochloride (0.75 g), and 1,4-dioxane (8 mL) was added sodium t-butoxide (0.45 g) under nitrogen atmosphere, and the mixture was stirred at 70° C. for 2 h. The reaction mixture was diluted with ethyl acetate and water, then the interlayer was removed by Celite filtration, and the organic layer was washed with saturated brine. The organic layer was dried with anhydrous magnesium sulfate, then the desiccant was removed by filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (silica gel, chloroform/methanol, and NH silica gel, ethyl acetate) to obtain colorless amorphous (S)-1-(3-(4,6-dimethylquinolin-2-ylamino)pyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone (0.30 g).

후처리

  1. customthe interlayer was removed by Celite filtration
  2. washthe organic layer was washed with saturated brine
  3. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  4. customthe desiccant was removed by filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (silica gel, chloroform/methanol, and NH silica gel, ethyl acetate)

출처 및 근거

ORD 기록
ord-5b126a486c4c452cad024b96b448d7a2
출처 데이터셋
uspto-grants-2011_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08044068B2

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