反应详情

After adding (1S)-(+)-10-camphorsulfonic acid (127 mg) to a solution of crude 3-[6-(4-aminophenoxy)pyrimidin-4-yl]-1-[1-(2-dimethylaminoethyl)piperidin-4-yl]-1-methylurea (119 mg) in ethanol (3.0 ml), the mixture was stirred for 15 minutes at room temperature. After then adding 2-(4-fluorophenyl)acetyl isothiocyanate (4.08 ml, 0.25 M solution in toluene) thereto, the mixture was stirred at room temperature for 2 hours. The reaction mixture was partitioned between saturated aqueous sodium hydrogencarbonate (10 ml) and ethyl acetate (30 ml). The organic layer was washed with brine and dried over anhydrous sodium sulfate. The dried organic layer was concentrated and the residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=20:1 to 10:1). Fractions containing the target compound were concentrated, and the residue was purified by LC-MS (water-acetonitrile-trifluoroacetic acid system). Fractions containing the target compound were concentrated, saturated aqueous sodium hydrogencarbonate was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was then dried over anhydrous sodium sulfate. The dried organic layer was concentrated. Diethyl ether was added to the obtained solid to produce a suspension. The resulting precipitate was filtered and then dried to provide the title compound (12.4 mg) as white powder.

1. customThe reaction mixture was partitioned between saturated aqueous sodium hydrogencarbonate (10 ml) and ethyl acetate (30 ml)
2. washThe organic layer was washed with brine
3. dry with materialdried over anhydrous sodium sulfate
4. concentrationThe dried organic layer was concentrated
5. customthe residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent
6. additionFractions containing the target compound
7. concentrationwere concentrated
8. customthe residue was purified by LC-MS (water-acetonitrile-trifluoroacetic acid system)
9. additionFractions containing the target compound
10. concentrationwere concentrated
11. additionsaturated aqueous sodium hydrogencarbonate was added to the residue
12. extractionthe mixture was extracted with ethyl acetate
13. dry with materialThe organic layer was then dried over anhydrous sodium sulfate
14. concentrationThe dried organic layer was concentrated
15. additionDiethyl ether was added to the obtained solid
16. customto produce a suspension
17. filtrationThe resulting precipitate was filtered
18. customdried