反应详情

THF (40 ml) was added to methyl 3-[3-bromo-4-(indan-2-yloxy)-5-nitrophenyl]propionate (14.00 g, prepared according to the method of International Patent Publication WO03/70686), 1-methyl-1H-indazol-5-boronic acid (7.62 g, prepared according to the method of International Patent Publication WO03/70686), palladium acetate (75 mg, Wako Pure Chemical Industries) and triphenylphosphine (0.17 g, Wako Pure Chemical Industries), and the mixture was stirred. Then, a solution dissolving tripotassium phosphate (16.97 g, Wako Pure Chemical Industries) in water (27 ml) was added to the above mixture, and the interior of the system was purged with nitrogen. Then, this mixture was stirred for 4 hours at 60° C. to allow the reaction. After confirming the completion of the reaction, the reaction solution was partitioned to obtain the upper layer. The upper layer was cooled to room temperature, ethyl acetate (40 ml) and activated carbon (2.8 g, Japan Envirochemicals) were added thereto, and the mixture was further stirred for 1 hour at room temperature. The suspension was filtered to obtain a filtrate, and the residue on the filter was washed with ethyl acetate (20 ml) to obtain the wash solution. The filtrate and the wash solution were combined and concentrated under reduced pressure to obtain a concentrate (44 g). Then, acetone (140 ml) was added to the concentrate. The mixture was stirred and water (140 ml) was added thereto over 1 hour with stirring. The mixture was further stirred for another 1 hour at room temperature. Then, this mixture was filtered, the solid on the filter was washed with water (70 ml), and wet solid was obtained. This wet solid was dried under reduced pressure at 50° C. to obtain crystals of methyl 3-[4-(indan-2-yloxy)-3-(1-methyl-1H-indazol-5-yl)-5-nitrophenyl]propionate (15.7 g).

1. customprepared
2. customprepared
3. additionwas added to the above mixture
4. customthe interior of the system was purged with nitrogen
5. stirringThen, this mixture was stirred for 4 hours at 60° C.
6. customthe reaction
7. customthe completion of the reaction
8. customthe reaction solution was partitioned
9. customto obtain the upper layer
10. stirringthe mixture was further stirred for 1 hour at room temperature
11. filtrationThe suspension was filtered
12. customto obtain a filtrate
13. washthe residue on the filter was washed with ethyl acetate (20 ml)
14. customto obtain the wash solution
15. concentrationconcentrated under reduced pressure
16. customto obtain
17. concentrationa concentrate (44 g)
18. additionThen, acetone (140 ml) was added to the concentrate
19. stirringThe mixture was stirred
20. additionwater (140 ml) was added
21. stirringover 1 hour with stirring
22. stirringThe mixture was further stirred for another 1 hour at room temperature
23. filtrationThen, this mixture was filtered
24. washthe solid on the filter was washed with water (70 ml)
25. customwet solid was obtained
26. customThis wet solid was dried under reduced pressure at 50° C.