反应详情

3-[4-(4-Aminophenoxy)pyridin-2-yl]-1-methyl-1-(1-methylpiperidin-4-yl)urea (60 mg) was dissolved in ethanol (1 ml) while stirring, and then D-10-camphorsulfonic acid (39.3 mg) was added thereto under a nitrogen atmosphere, followed by stirring for 5 min. Phenylacetyl isothiocyanate (toluene solution, 1.82 M, 0.074 ml) was added thereto, followed by stirring further for 1.5 hrs. The reaction mixture was partitioned between ethyl acetate (30 ml) and a saturated aqueous solution of sodium hydrogencarbonate (20 ml). The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, water and brine in this order, 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, eluent; hexane:ethyl acetate=1:5, then ethyl acetate). Fractions containing the crude product were concentrated to give a residue, which was then purified by LC-MS. The fractions containing the target compound were concentrated to give a residue, to which a saturated aqueous solution of sodium hydrogencarbonate was added to extract with ethyl acetate. The organic layer was separated, 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, eluent; ethyl acetate, then ethyl acetate:ethanol=9:1). Fractions containing the target compound were concentrated to give a residue, to which diethyl ether (0.3 ml)-hexane (0.1 ml) was then added to suspend. The solid was filtered off and dried under aeration to provide the titled compound (2.0 mg, 2.2%) as a white solid.

1. stirringby stirring for 5 min
2. stirringby stirring further for 1.5 hrs
3. customThe reaction mixture was partitioned between ethyl acetate (30 ml)
4. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, water and brine in this order
5. dry with materialdried over anhydrous sodium sulfate
6. customThe solvent was evaporated
7. customto give a residue, which
8. customwas then purified by silica gel column chromatography (Fuji Silysia NH, eluent
9. additionFractions containing the crude product
10. concentrationwere concentrated
11. customto give a residue, which
12. customwas then purified by LC-MS
13. additionThe fractions containing the target compound
14. concentrationwere concentrated
15. customto give a residue
16. extractionto extract with ethyl acetate
17. customThe organic layer was separated
18. dry with materialdried over anhydrous sodium sulfate
19. customThe solvent was evaporated
20. customto give a residue, which
21. customwas then purified by silica gel column chromatography (Fuji Silysia NH, eluent
22. additionFractions containing the target compound
23. concentrationwere concentrated
24. customto give a residue
25. filtrationThe solid was filtered off
26. customdried under aeration