反应详情

2-Amino-4-{2-fluoro-4-[3-(2-phenylacetyl)thioureido]phenoxy}pyridine (66.6 mg) was dissolved in tetrahydrofuran (2.0 ml) under a nitrogen atmosphere, and then N-methylmorpholine (0.0462 ml) and phenyl chloroformate (0.0527 ml) in this order were added dropwise thereto while cooling in an ice bath, followed by raising the temperature up to room temperature and stirring for 15 min. The solvent was evaporated to give a residue, which was dissolved in N,N-dimethylformamide (2.0 ml), and then 4-(pyrrolidin-1-yl)piperidine (136 mg) was added thereto at room temperature, followed by stirring for 2 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 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:methanol=95:5). 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 (46.3 mg, 48%) as white powder.

1. temperaturewhile cooling in an ice bath
2. customThe solvent was evaporated
3. customto give a residue, which
4. customat room temperature
5. stirringby stirring for 2 hr
6. customThe reaction mixture was partitioned between ethyl acetate
7. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine in this order
8. dry with materialdried over anhydrous sodium sulfate
9. customThe solvent was evaporated
10. customto give a residue, which
11. customwas then purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate:methanol=95:5)
12. additionFractions containing the target compound
13. concentrationwere concentrated under a reduced pressure
14. customto give a residue, which
15. customwas dried in vacuum