反应详情

To a solution of 1-(3-diethylaminopropyl)-3-[4-(4-amino-2-fluorophenoxy)pyridin-2-yl]-1-methylurea (100 mg) in tetrahydrofuran (2.0 ml) was added a solution of phenylacetyl isocyanate in hexane (3.4 ml, Production Example 1), followed by stirring under a nitrogen atmosphere at room temperature for 30 min. A solution of phenylacetyl isocyanate in hexane (1.0 ml, Production Example 1) was further added thereto, followed by stirring at room temperature for 30 min. The reaction mixture was partitioned between a mixed solvent of ethyl acetate-tetrahydrofuran (1:1, 200 ml) and a saturated aqueous solution of sodium hydrogencarbonate (15 ml). The organic layer was washed with a 1 N aqueous solution of sodium hydroxide, 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). Fractions containing a crude product were concentrated to give a residue, which was then dissolved in ethyl acetate and washed with a 1 N aqueous solution of sodium hydroxide. The organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, to which diethyl ether (3 ml) and hexane (3 ml) were then added to precipitate a solid. The solid was filtered off, washed with diethyl ether, and dried under aeration to provide the titled compound (8.3 mg, 5.9%) as colorless powder.

1. stirringby stirring at room temperature for 30 min
2. customThe reaction mixture was partitioned between a mixed solvent of ethyl acetate-tetrahydrofuran (1:1, 200 ml)
3. washThe organic layer was washed with a 1 N aqueous solution of sodium hydroxide
4. dry with materialdried over anhydrous sodium sulfate
5. customThe solvent was evaporated
6. customto give a residue, which
7. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate)
8. additionFractions containing a crude product
9. concentrationwere concentrated
10. customto give a residue, which
11. washwashed with a 1 N aqueous solution of sodium hydroxide
12. dry with materialThe organic layer was dried over anhydrous sodium sulfate
13. customThe solvent was evaporated
14. customto give a residue
15. customto precipitate a solid
16. filtrationThe solid was filtered off
17. washwashed with diethyl ether
18. customdried under aeration