1,4-Dioxane → 1-((3R,4R)-3-(6-hydroxy-4-methylquinolin-2-ylamino)-4-methoxypyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone

HRID 1666622노트

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HRID 1666622 반응식
Cl[C:2]1[CH:11]=[C:10]([CH3:12])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([OH:13])[CH:8]=2)[N:3]=1.[NH2:14][C@H:15]1[C@H:19]([O:20][CH3:21])[CH2:18][N:17]([C:22](=[O:35])[CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][C:31]([F:34])([F:33])[F:32])=[CH:26][CH:25]=2)[CH2:16]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]>[OH:13][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([NH:14][C@H:15]1[C@H:19]([O:20][CH3:21])[CH2:18][N:17]([C:22](=[O:35])[CH2:23][C:24]3[CH:25]=[CH:26][C:27]([O:30][C:31]([F:32])([F:33])[F:34])=[CH:28][CH:29]=3)[CH2:16]1)[CH:11]=[C:10]2[CH3:12]

참가 물질

8

반응물 4

HCID 312751,4-DioxaneHCID 7663822-Chloro-4-methyl-quinolin-6-olHCID 23676156Sodium t-butoxide2회HCID 579701661-((3R,4R)-3-amino-4-methoxypyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone

생성물 1

HCID 579702171-((3R,4R)-3-(6-hydroxy-4-methylquinolin-2-ylamino)-4-methoxypyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone수율 17.1%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매2회HCID 962Water용매HCID 8857Ethyl Acetate용매

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온도
65 °C

실험 절차

To a mixture of 2-chloro-6-hydroxy-4-methylquinoline (0.153 g), Pd2(dba)3 (0.036 g), (±)-BINAP (0.073 g), 1-((3R,4R)-3-amino-4-methoxypyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone (0.25 g), and 1,4-dioxane (7 mL) was added sodium t-butoxide (0.241 g) under nitrogen atmosphere, and the mixture was stirred at 65° C. for 3 h. Pd2(dba)3 (0.036 g), (±)-BINAP (0.073 g), and sodium t-butoxide (0.241 g) were further added, and the mixture was stirred at 65° C. for 5 h. The reaction mixture was diluted with ethyl acetate and water, then the interlayer was removed by Celite filtration, and the organic layer washed with saturated brine. The organic layer was dried with anhydrous magnesium sulfate, 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 1-((3R,4R)-3-(6-hydroxy-4-methylquinolin-2-ylamino)-4-methoxypyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone (0.064 g).

후처리

  1. stirringthe mixture was stirred at 65° C. for 5 h
  2. customthe interlayer was removed by Celite filtration
  3. washthe organic layer washed with saturated brine
  4. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  5. customthe desiccant was removed by filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. 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-63ef79ff1f8c4176ba55f51a60c5a080
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08044068B2

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