反应详情

A solution of (Z)-4-(3-aminophenyl)-1,3-dihydro-3-[(1H-pyrrol-2-yl)methylene]-2H-indol-2-one (30 mg, 0.100 mmol) (from Example 4 supra), crude (4-fluorosulfonyl-benzoylamino)-acetic acid (28 mg, 0.107 mmol) (from step B above), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU, 45 mg, 0.119 mmol) (Advance ChemTech), 1-hydroxybenzotriazole hydrate (HOBT, 16 mg, 0.118 mmol) (Aldrich), and N,N-diisopropylethylamine (52 μL, 0.300 mmol) (Aldrich) in 3 mL of dry N,N-dimethylformamide (Fisher Scientific) was stirred at 50° C. under a nitrogen atmosphere for 7 h then stirred at room temperature under a nitrogen atmosphere for 12 h. The reaction mixture was diluted with 40 mL ethyl acetate and washed with distilled water. The organic phase was concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 40% acetone-hexanes then 70% acetone-hexanes elution) provided pure (Z)-N-[2-[[3-[2,3-dihydro-2-oxo-3-[(1H-pyrrol-2-yl)methylene]-1H-indol-4-yl]phenyl]amino]-2-oxoethyl]-4-(fluorosulfonyl)benzamide (yield: 13 mg, 24%) as a yellow solid (mp 248-250° C.).

1. washwashed with distilled water
2. concentrationThe organic phase was concentrated in vacuo
3. washFlash chromatography (Merck Silica gel 60, 230-400 mesh, 40% acetone-hexanes then 70% acetone-hexanes elution)