反应详情

220 mg of 4-difluoromethoxy-2,3-dihydro-1H-indole (reference example 5d) and 364 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride are added to a solution of 237 mg of sodium [1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate (obtained in step 2d of example 4d) in 7 ml of N,N-dimethylformamide and 7 ml of pyridine. The reaction mixture is stirred at ambient temperature for 16 hours, and then 20 ml of water are added and the mixture is extracted with ethyl acetate. The organic phase is washed successively with a 0.1N hydrochloric acid solution, water and a saturated sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica column chromatography, elution being carried out with a mixture of dichloromethane and methanol (95/05: v/v), so as to give 110 mg of 2-[2-(4-difluoromethoxy-2,3-dihydroindol-1-yl)-2-oxoethyl]-3-methyl-6-morpholin-4-yl-3H-pyrimidin-4-one in the form of a pale pink solid, the characteristics of which are the following:

1. extractionthe mixture is extracted with ethyl acetate
2. washThe organic phase is washed successively with a 0.1N hydrochloric acid solution, water
3. dry with materiala saturated sodium chloride solution, dried over magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customThe residue is purified by silica column chromatography, elution
7. additionbeing carried out with a mixture of dichloromethane and methanol (95/05: v/v)