HOAt → (E)-2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-N-(1-(2,2,2-trifluoroethylcarbamoyl)cyclopropyl)benzamide

HRID 1503784ノート

反応式

HRID 1503784 の反応式
[Cl:1][C:2]1[CH:10]=[C:9](/[CH:11]=[CH:12]/[CH:13]([C:18]2[CH:23]=[C:22]([Cl:24])[C:21]([Cl:25])=[C:20]([Cl:26])[CH:19]=2)[C:14]([F:17])([F:16])[F:15])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[NH2:27][C:28]1([C:31]([NH:33][CH2:34][C:35]([F:38])([F:37])[F:36])=[O:32])[CH2:30][CH2:29]1.F[P-](F)(F)(F)(F)F.ClC1N(C)CC[NH+]1C.ON1C2N=CC=CC=2N=N1>C(Cl)Cl.CN(C=O)C.CN(C1C=CN=CC=1)C>[Cl:1][C:2]1[CH:10]=[C:9](/[CH:11]=[CH:12]/[CH:13]([C:18]2[CH:23]=[C:22]([Cl:24])[C:21]([Cl:25])=[C:20]([Cl:26])[CH:19]=2)[C:14]([F:16])([F:15])[F:17])[CH:8]=[CH:7][C:3]=1[C:4]([NH:27][C:28]1([C:31](=[O:32])[NH:33][CH2:34][C:35]([F:37])([F:38])[F:36])[CH2:30][CH2:29]1)=[O:6]

参加物

7

反応物 4

HCID 181649HOAtHCID 218684192-Chloro-1,3-dimethylimidazolidin-1-ium;hexafluorophosphateHCID 654644011-amino-N-(2,2,2-trifluoroethyl)cyclopropanecarboxamideHCID 86722568(E)-2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acid

生成物 1

HCID 86722567(E)-2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-N-(1-(2,2,2-trifluoroethylcarbamoyl)cyclopropyl)benzamide収率 75%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 22350042dichloromethane N,N-dimethylformamide溶媒

実験手順

To a stirred solution of (E)-2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acid (300 mg, 0.67 mmol) and 1-amino-N-(2,2,2-trifluoroethyl)cyclopropanecarboxamide (148 mg, 0.81 mmol) in DCM/DMF (5 mL, 1:1), 2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (CIP) (92 mg, 0.33 mmol), 1-hydroxy-7-azabenzotriazole (HOAt) (48 mg, 0.33 mmol) and DMAP (5 mol %) were added, and the resulting mixture was stirred at room temperature (RT) for 4 h. The reaction mixture was poured into ice-water and extracted with EtOAc. The organic phase was dried (Na2SO4), filtered, concentrated and the residue was purified by column chromatography on silica (100-200 mesh) eluting with 30% EtOAc in petroleum ether to give the title compound as pale yellow gum (300 mg, 75%). Characterization data for this molecule is listed in Table 2.

後処理

  1. extractionextracted with EtOAc
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customthe residue was purified by column chromatography on silica (100-200 mesh)
  6. washeluting with 30% EtOAc in petroleum ether

出典と根拠

ORDレコード
ord-1d76034e53a8425d884b4ca8f3e8a555
出典データセット
uspto-grants-2015_12
特許番号
US09212164B2

反応ノート

読み込み中…