反应详情

After dissolving 3-[6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl]-1-methyl-1-(1-methylpiperidin-4-yl)urea (70.3 mg) in ethanol (2 ml) under a nitrogen atmosphere, D-10-camphorsulfonic acid (43.7 mg) was added and the mixture was stirred for 5 minutes. A 0.24 M solution of 2-(4-fluorophenyl)acetyl isothiocyanate in toluene (1.02 ml) was added thereto, and the mixture was stirred for 17.5 hours. Then, a 0.24 M solution of 2-(4-fluorophenyl)acetyl isothiocyanate in toluene (0.3 ml) was further added to the reaction mixture, and stirring was continued for 30 minutes. Ethyl acetate (30 ml) and saturated aqueous sodium hydrogencarbonate (20 ml) were added to the reaction mixture for partition. The organic layer was washed with saturated aqueous sodium hydrogencarbonate (20 ml), water (20 ml) and brine (20 ml) and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:8), and then fractions containing the target compound were concentrated under reduced pressure. Diethyl ether (1 ml) and hexane (2 ml) were added to the resultant residue to produce a suspension. After filtering the solid, it was subjected to aeration drying to provide the title compound (39.4 mg, 36.8%) as pale yellow powder.

1. stirringthe mixture was stirred for 17.5 hours
2. stirringstirring
3. waitwas continued for 30 minutes
4. customfor partition
5. washThe organic layer was washed with saturated aqueous sodium hydrogencarbonate (20 ml), water (20 ml) and brine (20 ml)
6. dry with materialdried over anhydrous sodium sulfate
7. distillationThe solvent was distilled off under reduced pressure
8. customThe resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:8)
9. additionfractions containing the target compound
10. concentrationwere concentrated under reduced pressure
11. additionDiethyl ether (1 ml) and hexane (2 ml) were added to the resultant residue
12. customto produce a suspension
13. filtrationAfter filtering the solid, it
14. customdrying