反应详情

5 ml of pyridine, 404 mg of 4-(4-methylpiperazin-1-ylmethyl)-2,3-dihydro-1H-indole (reference example 9d) and 390 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride are successively added to a solution of 500 mg of sodium [1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate (example 4d, step 2d) in 5 ml of N,N-dimethylformamide. The reaction mixture is stirred at ambient temperature for 16 hours, and then concentrated under reduced pressure. The residue is taken up in 30 ml of saturated aqueous sodium chloride solution and then extracted with dichloromethane (3×30 ml). The organic phases are combined and then dried over magnesium sulfate, filtered through sintered glass and concentrated under reduced pressure. After purification of the residue by silica column chromatography, elution being carried out with a mixture of dichloromethane and 7N ammoniacal methanol (95/05), 40 mg of 3-methyl-2-(2-{4-[(4-methylpiperazin-1-yl)methyl]-2,3-dihydro-1H-indol-1-yl}-2-oxoethyl)-6-(morpholin-4-yl)pyrimidin-4(3H)-one are obtained in the form of a white solid, the characteristics of which are the following:

1. concentrationconcentrated under reduced pressure
2. extractionextracted with dichloromethane (3×30 ml)
3. dry with materialdried over magnesium sulfate
4. filtrationfiltered through sintered glass
5. concentrationconcentrated under reduced pressure
6. customAfter purification of the residue
7. washby silica column chromatography, elution
8. additionbeing carried out with a mixture of dichloromethane and 7N ammoniacal methanol (95/05), 40 mg of 3-methyl-2-(2-{4-[(4-methylpiperazin-1-yl)methyl]-2,3-dihydro-1H-indol-1-yl}-2-oxoethyl)-6-(morpholin-4-yl)pyrimidin-4(3H)-one
9. customare obtained in the form of a white solid