反应详情

To a solution of 4-(4-amino-3-fluorophenoxy)pyridin-2-ylamine (500 mg) in tetrahydrofuran (10 ml) was added triethylamine (0.223 ml), and then phenyl chloroformate (0.200 ml) was added thereto while stirring in an ice bath, followed by stirring under a nitrogen atmosphere for 2 hr. The reaction mixture was concentrated under a reduced pressure to give a residue, to which N,N-dimethylformamide (10 ml) and pyrrolidine (0.667 ml) were then added, followed by stirring at room temperature for 21 hrs. The reaction mixture was partitioned between ethyl acetate (100 ml) and water (100 ml). The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:2, ethyl acetate, then ethyl acetate:methanol=10:1). Fractions containing the target compound were concentrated to provide the titled compound (94 mg, 13%) as a purple oil.

1. stirringby stirring under a nitrogen atmosphere for 2 hr
2. concentrationThe reaction mixture was concentrated under a reduced pressure
3. customto give a residue
4. stirringby stirring at room temperature for 21 hrs
5. customThe reaction mixture was partitioned between ethyl acetate (100 ml) and water (100 ml)
6. washThe organic layer was washed with brine
7. dry with materialdried over anhydrous sodium sulfate
8. customThe solvent was evaporated
9. customto give a residue, which
10. customwas then purified by silica gel column chromatography (eluent
11. additionFractions containing the target compound
12. concentrationwere concentrated