反应详情

Diethyl azodicarboxylate (1.88 mL, 4.33 mmol) was added dropwise to a solution of N-[2,4-bis(methylthio)-6-methylpyridin-3-yl]-2-hydroxyacetamide (373 mg, 1.44 mmol), 1-[2-(benzimidazol-2-ylthio)ethyl]piperazine (1.40 g, 5.34 mmol), and triphenylphosphine (1.34 g, 5.09 mmol) in dimethylformamide (DMF) (20 mL) under stirring with water cooling over 5 minutes. The resultant mixture was stirred at room temperature for 60 minutes, and water (2 mL) was added thereto so as to deactivate the reagent. The reaction mixture was partitioned between 1N hydrochloric acid (30 mL) and ethyl acetate (30 mL). The formed organic layer was extracted with 1N hydrochloric acid (15 mL×2). The formed aqueous layers were combined, and the thus-combined aqueous layer was washed with ethyl acetate (20 mL×2). The pH of the resultant mixture was adjusted to 8 to 9 with 1N sodium hydroxide. The formed aqueous layer was extracted with ethyl acetate (20 mL×3). The organic layer was washed with saturated brine, and dried over sodium sulfate anhydrate, followed by solvent removal under reduced pressure. The residue was purified through silica gel column chromatography (developer: chloroform:methanol=100:3). The obtained oily substances were crystallyzed from ethanol and ether, to thereby yield 2-[4-[2-(benzimidazol-2-ylthio)ethyl]piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methylpyridin-3-yl]acetamide as colorless crystals (372 mg, yield: 51%).

1. customThe reaction mixture was partitioned between 1N hydrochloric acid (30 mL) and ethyl acetate (30 mL)
2. extractionThe formed organic layer was extracted with 1N hydrochloric acid (15 mL×2)
3. washthe thus-combined aqueous layer was washed with ethyl acetate (20 mL×2)
4. extractionThe formed aqueous layer was extracted with ethyl acetate (20 mL×3)
5. washThe organic layer was washed with saturated brine
6. dry with materialdried over sodium sulfate anhydrate
7. customfollowed by solvent removal under reduced pressure
8. customThe residue was purified through silica gel column chromatography (developer: chloroform:methanol=100:3)