反应详情

A 50% aqueous solution (2.0 mL) of hydroxylamine was added, under ice cooling, to a methanol (4.0 mL) solution of 1-[(cyclopropylamino)methyl]-4-[(1E)-4-(4-{[1-methoxy-3-(methylamino)-1,3-dioxopropan-2-yl](methyl)carbamoyl}phenyl)but-1-en-3-yn-1-yl]benzene (0.18 g) as obtained in Example 23-(4), and the mixture was stirred for 25 minutes under ice cooling and then stirred for 1.5 hours under water cooling. Ethyl acetate and water were added to the reaction mixture to isolate the organic layer, and the extract was washed with water. The washed extract was dried over anhydrous sodium sulfate, the desiccant was filtered out, and the solvent was distilled off under reduced pressure. The resulting residue was purified by OH type silica gel column chromatography (gradient elution with chloroform/methanol=50/1→10/1), and further purified by preparative silica gel thin-layer chromatography (chloroform/methanol=10/1) to obtain 2-[({4-[(3E)-4-{4-[(cyclopropylamino)methyl]phenyl}but-3-en-1-yn-1-yl]phenyl}carbonyl)(methyl)amino]-N-hydroxy-N′-methylpropanediamide (Compound 481, light yellow solid) (41 mg, 23%).

1. customas obtained in Example 23-(4)
2. stirringstirred for 1.5 hours under water cooling
3. customto isolate the organic layer
4. washthe extract was washed with water
5. extractionThe washed extract
6. dry with materialwas dried over anhydrous sodium sulfate
7. filtrationthe desiccant was filtered out
8. distillationthe solvent was distilled off under reduced pressure
9. customThe resulting residue was purified by OH type silica gel column chromatography (gradient elution with chloroform/methanol=50/1→10/1)
10. customfurther purified by preparative silica gel thin-layer chromatography (chloroform/methanol=10/1)