反应详情

A mixture of ethyl 4-[2,4-dichloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate (Reference Example 33; 1.50 g, 4.04 mmol), 4-methyl-6-pyrrolidin-1-ylpyridin-3-amine (1.44 g, 8.09 mmol) and p-toluenesulfonic acid monohydrate (695 mg, 4.04 mmol) in 1-methyl-2-pyrrolidinone (8 mL) was irradiated by microwave at 180° C. for 110 min. After cooling, the mixture was diluted with ethyl acetate, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 20-100% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give a solid, which was recrystallized from ethyl acetate/isopropyl ether to give the title compound (745 mg, 1.46 mmol, 36%) as a colorless solid.

1. customwas irradiated by microwave at 180° C. for 110 min
2. temperatureAfter cooling
3. washwashed with water and brine
4. dry with materialdried over anhydrous magnesium sulfate
5. concentrationconcentrated in vacuo
6. customThe residue was purified by flash chromatography on silica gel eluting with a 20-100% ethyl acetate/n-hexane gradient mixture
7. concentrationThe filtrate was concentrated in vacuo
8. customto give a solid, which
9. customwas recrystallized from ethyl acetate/isopropyl ether