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

HRID 1666622ノート

反応式

HRID 1666622 の反応式
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]

参加物

8

反応物 4

HCID 312751,4-DioxaneHCID 7663822-Chloro-4-methyl-quinolin-6-olHCID 23676156Sodium t-butoxide2 回HCID 579701661-((3R,4R)-3-amino-4-methoxypyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone

生成物 1

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

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒2 回HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
65 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-63ef79ff1f8c4176ba55f51a60c5a080
出典データセット
uspto-grants-2011_10
特許番号
US08044068B2

反応ノート

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