反应详情

mCBPA (21 g of about 50% pure material, 61 mmol) was added to a solution of 1-{[7-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]methyl}cyclopentanol (18.89 g, 46.6 mmol) in chloroform (190 mL), and the reaction was stirred for one hour at room temperature. Additional mCPBA (11 g) was added, and the reaction was stirred for an additional 30 minutes. Concentrated ammonium hydroxide (40 mL) was added slowly followed by p-toluenesulfonyl chloride (9.32 g, 48.9 mmol). The reaction was stirred for one hour at room temperature, and additional chloroform (600 mL) was added. The reaction was stirred for one additional hour, and additional p-toluenesulfonyl chloride (4.45 g, 23.3 mmol) and ammonium hydroxide (10 mL) were added. After the reaction mixture was stirred for an additional 1.5 hours, it was filtered to remove a precipitate. The filtrate layers were separated, and the organic phase was washed with saturated aqueous sodium bicarbonate (2×200 mL), dried over sodium sulfate, and concentrated under reduced pressure. The residue (25.86 g) was triturated with acetonitrile at 98° C., and a solid impurity was removed by filtration. The acetonitrile was removed under reduced pressure, and the residue was dissolved in chloroform. The resulting solution was washed with 1% aqueous sodium carbonate, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluting with 98.5:1.5 chloroform:methanol) and then triturated with acetonitrile at 98° C., isolated by filtration at room temperature, and dried in a vacuum oven at 110° C. over two nights to provide 4.83 g of 1-{[4-amino-7-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]methyl}cyclopentanol as a white solid, mp 166-167.5° C.

1. stirringthe reaction was stirred for an additional 30 minutes
2. stirringThe reaction was stirred for one hour at room temperature
3. additionwere added
4. stirringAfter the reaction mixture was stirred for an additional 1.5 hours
5. filtrationit was filtered
6. customto remove a precipitate
7. customThe filtrate layers were separated
8. washthe organic phase was washed with saturated aqueous sodium bicarbonate (2×200 mL)
9. dry with materialdried over sodium sulfate
10. concentrationconcentrated under reduced pressure
11. customThe residue (25.86 g) was triturated with acetonitrile at 98° C.
12. customa solid impurity was removed by filtration
13. customThe acetonitrile was removed under reduced pressure
14. dissolutionthe residue was dissolved in chloroform
15. washThe resulting solution was washed with 1% aqueous sodium carbonate
16. dry with materialdried over sodium sulfate
17. filtrationfiltered
18. concentrationconcentrated under reduced pressure
19. customThe residue was purified by column chromatography on silica gel (eluting with 98.5:1.5 chloroform:methanol)
20. customtriturated with acetonitrile at 98° C.
21. customisolated by filtration at room temperature
22. customdried in a vacuum oven at 110° C. over two nights