反应详情

[6-(2-Fluoro-4-nitrophenoxy)pyrimidin-4-yl]carbamic acid phenyl ester (200 mg) was dissolved in tetrahydrofuran (16 ml), and then 1-methyl-4-(methylamino)piperidine (0.236 ml) was added thereto while stirring, followed by stirring for 20 min. The reaction mixture was partitioned between ethyl acetate (30 ml) and a saturated aqueous solution of sodium hydrogencarbonate (20 ml). The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (20 ml), water (20 ml) and brine (20 ml) in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a crude product (218 mg) of 3-[6-(2-fluoro-4-nitrophenoxy)pyrimidin-4-yl]-1-methyl-1-(1-methylpiperidin-4-yl)urea. The crude product (218 mg) was dissolved in methanol (5 ml)-tetrahydrofuran (5 ml), and then 10% palladium carbon (115 mg) was added thereto under a nitrogen atmosphere, followed by replacing with hydrogen inside the system and stirring for 3 hrs. The reaction mixture was filtered to remove the catalyst, which was washed with ethanol. The filtrate was concentrated under a reduced pressure to give a residue, which was then suspended in diethyl ether (2 ml)-hexane (4 ml). The solid was filtered off and dried under aeration to provide the titled compound (91.0 mg, 45%) as yellow powder.

1. stirringby stirring for 20 min
2. customThe reaction mixture was partitioned between ethyl acetate (30 ml)
3. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (20 ml), water (20 ml) and brine (20 ml) in this order
4. dry with materialdried over anhydrous sodium sulfate
5. customThe solvent was evaporated
6. customto give a crude product (218 mg) of 3-[6-(2-fluoro-4-nitrophenoxy)pyrimidin-4-yl]-1-methyl-1-(1-methylpiperidin-4-yl)urea
7. stirringstirring for 3 hrs
8. filtrationThe reaction mixture was filtered
9. customto remove the catalyst, which
10. washwas washed with ethanol
11. concentrationThe filtrate was concentrated under a reduced pressure
12. customto give a residue, which
13. filtrationThe solid was filtered off
14. customdried under aeration