反应详情

To 100 mg (0.256 mmol) tert-butyl 3-amino-5-(3,5-dicyano-2,6-dimethyl-1,4-dihydropyridin-4-yl)-1H-indazole-1-carboxylate (Example 3A) in dichloromethane (4 ml) were added 123 mg (0.77 mmol) 2-methoxyethanesulfonyl chloride and 0.11 ml (0.77 mmol) triethylamine. The mixture was stirred at room temperature for 12 h and then concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with brine. The aqueous layer was re-extracted with ethyl acetate, and the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was dissolved in dichloromethane (4 ml), and to the solution were added 0.175 ml (2.27 mmol) trifluoroacetic acid. The mixture was stirred at room temperature for 2 h and then concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with saturated aqueous sodium bicarbonate solution. The organic layer was separated, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by preparative RP-HPLC (acetonitrile/water gradient) to give 32 mg (30% of th.) of the title compound.

1. concentrationconcentrated under reduced pressure
2. dissolutionThe residue was dissolved in ethyl acetate
3. washwashed with brine
4. extractionThe aqueous layer was re-extracted with ethyl acetate
5. washthe combined organic layers were washed with brine
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. dissolutionThe residue was dissolved in dichloromethane (4 ml)
10. stirringThe mixture was stirred at room temperature for 2 h
11. concentrationconcentrated under reduced pressure
12. dissolutionThe residue was dissolved in ethyl acetate
13. washwashed with saturated aqueous sodium bicarbonate solution
14. customThe organic layer was separated
15. dry with materialdried over sodium sulfate
16. filtrationfiltered
17. concentrationconcentrated under reduced pressure
18. customThe residue was purified by preparative RP-HPLC (acetonitrile/water gradient)