1,1'-Carbonyldiimidazole → N-(benzylsulfonyl)-3-[4-({[4'-(2-ethoxyethoxy)-2',6'-dimethylbiphenyl-3-yl]methyl}amino)-2-fluorophenyl]propanamide

HRID 508050ノート

反応式

HRID 508050 の反応式
[CH2:1]([O:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[C:11]([CH3:13])[C:10]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][NH:21][C:22]3[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][C:30]([OH:32])=O)=[C:24]([F:33])[CH:23]=3)[CH:15]=2)=[C:9]([CH3:34])[CH:8]=1)[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[C:47]1([CH2:53][S:54]([NH2:57])(=[O:56])=[O:55])[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1.C1CCN2C(=NCCC2)CC1>O1CCCC1>[CH2:53]([S:54]([NH:57][C:30](=[O:32])[CH2:29][CH2:28][C:25]1[CH:26]=[CH:27][C:22]([NH:21][CH2:20][C:16]2[CH:15]=[C:14]([C:10]3[C:9]([CH3:34])=[CH:8][C:7]([O:6][CH2:5][CH2:4][O:3][CH2:1][CH3:2])=[CH:12][C:11]=3[CH3:13])[CH:19]=[CH:18][CH:17]=2)=[CH:23][C:24]=1[F:33])(=[O:56])=[O:55])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1

参加物

6

反応物 4

HCID 682631,1'-CarbonyldiimidazoleHCID 78318BenzenemethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 231572823-[4-({[4'-(2-Ethoxyethoxy)-2',6'-dimethylbiphenyl-3-yl]methyl}amino)-2-fluorophenyl]propanoic acid

生成物 1

HCID 23157485N-(benzylsulfonyl)-3-[4-({[4'-(2-ethoxyethoxy)-2',6'-dimethylbiphenyl-3-yl]methyl}amino)-2-fluorophenyl]propanamide収率 76.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 3-[4-({[4′-(2-ethoxyethoxy)-2′,6′-dimethylbiphenyl-3-yl]methyl}amino)-2-fluorophenyl]propanoic acid (0.186 g, 0.400 mmol) in tetrahydrofuran (5 mL) was added 1,1′-carbonyldiimidazole (97.3 mg, 0.600 mmol), and the mixture was heated under reflux under a nitrogen atmosphere for 1 hr. After cooling the reaction mixture, 1-phenylmethanesulfonamide (91.5 mg, 0.480 mmol) and 1,8-diazabicyclo[5.4.0]-7-undecene (0.0897 mL, 0.600 mmol) were added, and the mixture was stirred under a nitrogen atmosphere at room temperature for 24 hr. The reaction mixture was concentrated under reduced pressure, 10% aqueous citric acid solution was added to the residue, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (20%-60% ethyl acetate/hexane) to give the title compound (0.189 g, yield 76%) as a colorless oil.

後処理

  1. temperaturethe mixture was heated
  2. temperatureunder reflux under a nitrogen atmosphere for 1 hr
  3. additionwere added
  4. concentrationThe reaction mixture was concentrated under reduced pressure, 10% aqueous citric acid solution
  5. additionwas added to the residue
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe extract was washed with saturated brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (20%-60% ethyl acetate/hexane)

出典と根拠

ORDレコード
ord-5e0cc7535ac74f00904b78326ec0eba7
出典データセット
uspto-grants-2010_08
特許番号
US07786165B2

反応ノート

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