反应详情

To a solution of 1-[4-(2-aminopyridin-4-yloxy)-2-fluorophenyl]-3-[2-(4-fluorophenyl)acetyl]thiourea (26 mg) in tetrahydrofuran (2.0 ml) were added triethylamine (0.0175 ml) and phenyl chloroformate (0.0118 ml) in this order under a nitrogen atmosphere, followed by stirring at room temperature for 10 min. The solution was concentrated under a reduced pressure to give a residue, which was then dissolved in N,N-dimethylformamide (1.0 ml). Triethylamine (0.0873 ml) and dimethylamine hydrochloride (25.6 mg) were then added thereto, followed by stirring at room temperature for 24 hrs. To the reaction mixture was added water (30 ml) and ethyl acetate (50 ml), followed by stirring at room temperature for 4 hrs. The organic layer was separated, washed with brine (30 ml), 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, heptane:ethyl acetate=1:2, ethyl acetate, then ethyl acetate:methanol=20:1). Fractions containing the target compound were concentrated to give a residue, which was purified again by silica gel column chromatography (eluent; heptane:ethyl acetate=1:2, ethyl acetate, then ethyl acetate:methanol=20:1). Fractions containing the target compound were concentrated to give a pale yellow solid (83.7 mg), which was suspended in ethyl acetate (1 ml) and hexane (3 ml). The solid was filtered off and dried under aeration to provide the titled compound (4.8 mg, 15.8%) as colorless powder.

1. concentrationThe solution was concentrated under a reduced pressure
2. customto give a residue, which
3. stirringby stirring at room temperature for 24 hrs
4. stirringby stirring at room temperature for 4 hrs
5. customThe organic layer was separated
6. washwashed with brine (30 ml)
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 (Fuji Silysia NH, heptane
11. additionFractions containing the target compound
12. concentrationwere concentrated
13. customto give a residue, which
14. customwas purified again by silica gel column chromatography (eluent
15. additionFractions containing the target compound
16. concentrationwere concentrated