反应详情

To a 0.76M solution of isopropylmagnesium bromide in THF (2.0 ml) was added a solution of 5-(4-{2-[(aminocarbonyl)-amino]ethyl}phenyl)-N-methoxy-1-(4-methoxyphenyl)-N-methyl-1H-pyrazole-3-carboxamide (130 mg) in THF (2 ml) dropwise at at 4° C. The mixture was stirred at ambient temperature overnight. Additional 0.76M solution of isopropylmagnesium bromide in THF (2.0 ml) was added and the mixture was stirred at 50° C. for 5 hours. The reaction mixture was cooled to ambient temperature and was quenched by adding saturated aqueous ammonium chloride solution. The mixture was extracted with AcOEt. The organic layer was washed with 1M HCl, saturated aqueous sodium bicarbonate solution, saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by preparative thin layer silica gel chromatography developed by MeOH/CHC3 10%. The separated silica gel was extracted with 10% MeOH/CHCl3 and the solvent was evaporated in vacuo to give N-(2-{4-[3-isobutyryl-1-(4-methoxyphenyl)-1H-pyrazol-5-yl]phenyl}ethyl)urea (30 mg) as amorphous powder.

1. stirringthe mixture was stirred at 50° C. for 5 hours
2. temperatureThe reaction mixture was cooled to ambient temperature
3. customwas quenched
4. additionby adding saturated aqueous ammonium chloride solution
5. extractionThe mixture was extracted with AcOEt
6. washThe organic layer was washed with 1M HCl, saturated aqueous sodium bicarbonate solution, saturated aqueous sodium chloride solution
7. dry with materialdried over magnesium sulfate
8. concentrationconcentrated in vacuo
9. customThe residue was purified by preparative thin layer silica gel chromatography
10. extractionThe separated silica gel was extracted with 10% MeOH/CHCl3
11. customthe solvent was evaporated in vacuo