反应详情

温度

150 °C

A mixture of ethyl 4-[2,4-dichloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate (Reference Example 33; 371 mg, 1.00 mmol), 4-amino-1,3,5-trimethylpyrazole (375 mg, 3.00 mmol) and p-toluenesulfonic acid monohydrate (190 mg, 1.00 mmol) in 1-methyl-2-pyrrolidinone (3 mL) was stirred at 150° C. for 16 hr. 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 0-5% methanol/ethyl acetate gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was recrystallized from ethyl acetate/n-hexane to give the title compound (340 mg, 0.74 mmol, 74%) as a colorless solid.

1. temperatureAfter cooling
2. extractionthe mixture was extracted with ethyl acetate
3. washOrganic layer was washed with water and brine
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationconcentrated in vacuo
6. customThe residue was purified by flash chromatography on silica gel eluting with a 0-5% methanol/ethyl acetate gradient mixture
7. concentrationThe filtrate was concentrated in vacuo
8. customto give the solid, which
9. customwas recrystallized from ethyl acetate/n-hexane