反应详情

3-[4-(4-Amino-2-fluorophenoxy)pyridin-2-yl]-1-methyl-1-(1-methylpiperidin-4-yl)urea (50.0 mg) was dissolved in tetrahydrofuran (2 ml) under a nitrogen atmosphere, and then a solution of phenylacetyl isocyanate in toluene (0.80 ml, 0.5 M solution in toluene, Production Example 1) was added thereto, followed by stirring for 1 hr. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate:ethanol=9:1) Fractions containing the target compound were concentrated to give a residue, to which diethyl ether (1 ml)-hexane (0,5 ml) was added to suspend. The solid was filtered off and dried under aeration to provide the titled compound (63.1 mg, 88.1%) as a pale yellow solid.

1. customThe reaction mixture was partitioned between ethyl acetate
2. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, water and brine in this order
3. dry with materialdried over anhydrous sodium sulfate
4. customThe solvent was evaporated
5. customto give a residue, which
6. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate:ethanol=9:1) Fractions
7. additioncontaining the target compound
8. concentrationwere concentrated
9. customto give a residue
10. filtrationThe solid was filtered off
11. customdried under aeration