反应详情

2-Amino-4-{2-fluoro-4-[3-(2-phenylacetyl)thioureido]phenoxy}pyridine (100 mg) was dissolved in tetrahydrofuran (2.5 ml) under a nitrogen atmosphere, and then N-methylmorpholine (0.080 ml) and phenyl chloroformate (0.080 ml) were added dropwise thereto while cooling in an ice bath, followed by raising the temperature up to room temperature and stirring for 20 min. 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 and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then dissolved in N,N-dimethylformamide (2.5 ml), and then N-methylmorpholine (0.2 ml) and 4-oxopiperidine hydrochloride monohydrate (272 mg) were added thereto at room temperature, followed by stirring for 23 hrs. 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 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 (eluent; ethyl acetate). Fractions containing the target compound were concentrated under a reduced pressure to give a residue, which was dried in vacuum to provide the titled compound (83.1 mg, 63%) as white powder.

1. temperaturewhile cooling in an ice bath
2. customThe reaction mixture was partitioned between ethyl acetate
3. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine in this order
4. dry with materialdried over anhydrous sodium sulfate
5. customThe solvent was evaporated
6. customto give a residue, which
7. customat room temperature
8. stirringby stirring for 23 hrs
9. customThe reaction mixture was partitioned between ethyl acetate
10. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine in this order
11. dry with materialdried over anhydrous sodium sulfate
12. customThe solvent was evaporated
13. customto give a residue, which
14. customwas then purified by silica gel column chromatography (eluent; ethyl acetate)
15. additionFractions containing the target compound
16. concentrationwere concentrated under a reduced pressure
17. customto give a residue, which
18. customwas dried in vacuum