反应详情

To a solution of 4-(1-methylazetidin-3-yl)piperazine-1-carboxylic acid [4-(4-amino-2-fluorophenoxy)pyridin-2-yl]amide (76 mg) in ethanol (2.0 ml) was added (1S)-(+)-10-camphorsulfonic acid (83.9 mg), followed by stirring at room temperature for 15 min. A solution of 2-phenylacetyl isothiocyanate in toluene (0.25 M, 2.28 ml) was added to the reaction mixture, followed by stirring at room temperature for 2 hrs. Ethyl acetate (50 ml) and a saturated aqueous solution of sodium hydrogencarbonate (20 ml) were added to the reaction mixture, and the organic layer was separated. 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, then ethyl acetate:methanol=20:1). Fractions containing a target compound were concentrated to give crystals, which were suspended in diethyl ether (5 ml). Then the crystals were filtered off, washed with hexane, and dried under aeration to provide the titled compound (32.1 mg, 29%) as colorless crystals.

1. stirringby stirring at room temperature for 2 hrs
2. customthe organic layer was separated
3. extractionThe aqueous layer was extracted with ethyl acetate
4. washThe combined organic layer was washed with brine
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationThe organic layer was concentrated
7. customto give a residue, which
8. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent
9. additionFractions containing a target compound
10. concentrationwere concentrated
11. customto give crystals, which
12. filtrationThen the crystals were filtered off
13. washwashed with hexane
14. customdried under aeration