反应详情

A mixture of ethyl 4-[2,4-dichloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate (Reference Example 33; 472 mg, 1.27 mmol), N2,N2,4-trimethylpyridine-2,5-diamine (580 mg, 3.81 mmol) and p-toluenesulfonic acid monohydrate (241 mg, 1.27 mmol) in 1-methyl-2-pyrrolidinone (4 mL) was irradiated by microwave at 180° C. for 135 min. After cooling, aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate. Organic layer was washed with water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 20-80% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give a solid, which was recrystallized from ethyl acetate/n-hexane to give the title compound (266 mg, 0.547 mmol, 43%) as a colorless solid.

1. customwas irradiated by microwave at 180° C. for 135 min
2. temperatureAfter cooling
3. extractionthe mixture was extracted with ethyl acetate
4. washOrganic layer was washed with water and brine
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated in vacuo
7. customThe residue was purified by flash chromatography on silica gel eluting with a 20-80% ethyl acetate/n-hexane gradient mixture
8. concentrationThe filtrate was concentrated in vacuo
9. customto give a solid, which
10. customwas recrystallized from ethyl acetate/n-hexane