反应详情

To a solution of 4-(3-dimethylaminoazetidin-1-yl)piperidine-1-carboxylic acid [4-(4-aminophenoxy)pyridin-2-yl]amide (60 mg) in tetrahydrofuran (5.0 ml) was added a solution of 2-(4-fluorophenyl)acetyl isocyanate in tetrahydrofuran (0.25 M, 1.75 ml) at room temperature, followed by stirring at room temperature for 0.5 hr. To the reaction mixture was added a saturated aqueous solution of sodium hydrogencarbonate, followed by stirring at room temperature for 0.5 hr. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The organic layer was concentrated to give a residue, which was then purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=10:1). Fractions containing a target compound were concentrated to give a solid, which was suspended in diethyl ether (1 ml) and hexane (2 ml). The solid was filtered off, washed with diethyl ether:hexane=1:2, and dried under aeration to provide the titled compound (23.2 mg, 27%) as white powder.

1. stirringby stirring at room temperature for 0.5 hr
2. extractionThe reaction mixture was extracted with ethyl acetate
3. washThe organic layer was washed with brine
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationThe organic layer was concentrated
6. customto give a residue, which
7. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent
8. additionFractions containing a target compound
9. concentrationwere concentrated
10. customto give a solid, which
11. filtrationThe solid was filtered off
12. washwashed with diethyl ether
13. dry with materialhexane=1:2, and dried under aeration