反应详情

1 g (2 mmol) of 2-hydroxyethyl-4-({[(4-chloro-2-methylphenyl)amino]carbonyl}amino)-1-[4-(trifluoromethyl)benzyl]-1H-imidazole-2-carboxylate (Example 125) are dissolved in a mixture of 25 ml of dichloromethane and 12 ml of DMF, and 1570 μl (1.14 g, 11.2 mmol) of triethylamine are added. While cooling in ice, 804 μl (1.52 g, 9.6 mmol) of bromoacetyl chloride and a catalytic amount of DMAP are added. After stirring at RT for 16 h, a further 0.57 g (5.6 mmol) of triethylamine, 0.76 g (4.8 mmol) of bromoacetyl chloride and a few crystals of DMAP are added while cooling in ice. The reaction mixture is stirred at RT for 2.5 h, poured into saturated sodium bicarbonate solution and extracted twice with ethyl acetate. The combined extracts are washed twice with water and once with saturated sodium chloride solution, dried with magnesium sulphate and evaporated in vacuo. The residue from evaporation is purified by chromatography on silica gel with dichloromethane/methanol as eluent.

1. additionare added
2. temperatureWhile cooling in ice
3. temperaturewhile cooling in ice
4. stirringThe reaction mixture is stirred at RT for 2.5 h
5. extractionextracted twice with ethyl acetate
6. washThe combined extracts are washed twice with water and once with saturated sodium chloride solution
7. dry with materialdried with magnesium sulphate
8. customevaporated in vacuo
9. customThe residue from evaporation
10. customis purified by chromatography on silica gel with dichloromethane/methanol as eluent