反应详情

Diisopropyl azodicarboxylate (0.770 mL, 1.52 mmol) was added dropwise to a solution of N-[2,4-bis(methylthio)-6-methylpyridin-3-yl]-2-hydroxyacetamide (131 mg, 0.508 mmol), 1-[2-(benzimidazol-2-ylthio)ethyl]piperazine iodate (933 mg, 1.88 mmol) and triphenylphosphine (470 mg, 1.79 mmol) in dimethylformamide (3 mL) under stirring with water cooling over 5 minutes. The resultant mixture was stirred at room temperature for 60 minutes, and water (10 mL) was added thereto. Subsequently, 1 mol/L hydrochloric acid (10 mL) and ethyl acetate (30 mL) were added the reaction mixture, to thereby collect the aqueous layer. The organic layer was extracted with 1 mol/L hydrochloric acid (10 mL×2). The obtained aqueous layers were combined, and the thus-combined aqueous layer was washed with ethyl acetate (30 mL×2). The pH of the resultant mixture was adjusted to 8 to 9 with a 1 mol/L aqueous sodium hydroxide solution, followed by extraction with ethyl acetate (30 mL×3). The organic layers were combined, and the thus-combined organic layer was washed with saturated brine. The thus-washed organic layer was dried over sodium sulfate anhydrate, and the solvent was removed under reduced pressure. The crude product was purified through silica gel column chromatography (silica gel: 40 g, developer: chloroform:methanol=100:3), to thereby yield 2-[4-[2-(benzimidazol-2-ylthio)ethyl]piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methylpyridin-3-yl]acetamide (240 mg, yield: 94%).

1. customto thereby collect the aqueous layer
2. extractionThe organic layer was extracted with 1 mol/L hydrochloric acid (10 mL×2)
3. washthe thus-combined aqueous layer was washed with ethyl acetate (30 mL×2)
4. extractionfollowed by extraction with ethyl acetate (30 mL×3)
5. washthe thus-combined organic layer was washed with saturated brine
6. dry with materialThe thus-washed organic layer was dried over sodium sulfate anhydrate
7. customthe solvent was removed under reduced pressure
8. customThe crude product was purified through silica gel column chromatography (silica gel: 40 g, developer: chloroform:methanol=100:3)