反应详情

Sodium hydrogen sulfide (1.07 g) was dissolved in N,N-dimethylformamide (25 ml). To the mixture was added 4N hydrogen chloride in ethylacetate (13.3 ml) at room temperature. After stirring for approximately 30 minutes at the same temperature, to the resulting mixture were added 4-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-6-methanesulfinyl-pyrimidin-2-ylamine (1.20 g) obtained in Step 5 of Example 314 and N,N-diisopropylethylamine (2.9 ml) successively. The mixture was stirred at 80° C. for four hours, and then the mixture was allowed to cool to room temperature. To the mixture were added to 2-chloro-ethylurea (3.20 g), N,N-diisopropylethylamine (5.8 ml) and N,N-dimethylformamide (15 ml) successively. The reaction mixture was stirred at 80° C. for 14 hours and then allowed to cool to room temperature. The reaction was quenched by adding water and extracted with ethyl acetate. The organic layer was separated, washed with water and brine subsequently, dried over anhydrous sodium sulfate. After removal of inorganic salts, the solution was concentrated by evaporation. The resulting residue was purified by HPLC (column; ODS, mobile phase; 0.05% TFA in water: 0.05% TFA in acetonitrile=65:35) to give {2-[2-amino-6-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-pyrimidin-4-ylsulfanyl]-ethyl}-urea (0.93 g).

1. stirringThe mixture was stirred at 80° C. for four hours
2. stirringThe reaction mixture was stirred at 80° C. for 14 hours
3. temperatureto cool to room temperature
4. customThe reaction was quenched
5. additionby adding water
6. extractionextracted with ethyl acetate
7. customThe organic layer was separated
8. washwashed with water and brine subsequently
9. dry with materialdried over anhydrous sodium sulfate
10. customAfter removal of inorganic salts
11. concentrationthe solution was concentrated by evaporation
12. customThe resulting residue was purified by HPLC (column; ODS, mobile phase; 0.05% TFA in water: 0.05% TFA in acetonitrile=65:35)