反应详情

To a solution of 4-(3-dimethylaminoazetidin-1-yl)piperidine-1-carboxylic acid [4-(4-amino-2-fluorophenoxy)pyridin-2-yl]amide (78 mg) in tetrahydrofuran (6.0 ml) was added a solution of 2-phenylacetyl isocyanate in hexane (0.25 M, 1.82 ml), followed by stirring at room temperature for 11 hrs. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The aqueous layer was extracted with ethyl acetate. The combined 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:methanol=100:7). Fractions containing a target compound were concentrated to give a residue, to which diethyl ether (2 ml) and hexane (2 ml) were added to give a precipitate. The precipitate was suspended in the solvent. Then the precipitate was filtered off, washed with diethyl ether, and dried under aeration to provide the titled compound (34.9 mg, 33%) as pale yellow powder.

1. customThe reaction mixture was partitioned between ethyl acetate
2. extractionThe aqueous layer was extracted with ethyl acetate
3. washThe combined 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; ethyl acetate:methanol=100:7)
8. additionFractions containing a target compound
9. concentrationwere concentrated
10. customto give a residue
11. customto give a precipitate
12. filtrationThen the precipitate was filtered off
13. washwashed with diethyl ether
14. customdried under aeration