反应详情

3-Chloroperoxybenzoic acid (mCPBA) (1.4 g of 77% pure material, 4.74 mmol) was added over a period of five minutes to a solution of 7-(benzyloxy)-2-(chloromethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinoline (2.0 g, 4.74 mmol) in chloroform (47 mL); the reaction mixture was stirred at ambient temperature for one hour. The reaction solution was partitioned between chloroform (50 mL) and saturated aqueous sodium carbonate (50 mL). The layers were separated and the aqueous layer extracted with chloroform (50 mL). The organic layers were combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford an oil. To the crude N-oxide dissolved in dichloromethane (24 mL) was added ammonium hydroxide (8 mL), and then p-toluenesulfonyl chloride (1.0 g, 3.11 mmol) was added in portions over a period of 2 minutes. The reaction mixture was stirred at ambient temperature for one hour, and then saturated aqueous sodium carbonate (50 mL) and chloroform (50 mL) were added. The aqueous layer was separated and extracted with chloroform (50 mL). The combined organic fractions were dried over sodium sulfate, filtered, and concentrated under reduced pressure to provide 2.1 g of crude product as a tan solid. The crude product was purified by column chromatography using a HORIZON HPFC system (an automated, modular high-performance flash purification product available from Biotage, Inc, Charlottesville, Va., USA) using a FLASH 40+M silica cartridge (also available from Biotage, Inc.) (eluting with dichloromethane:methanol in a gradient from 100:0 to 90:10) to provide 1.8 g of 7-(benzyloxy)-2-(chloromethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine as a tan solid.

1. customThe reaction solution was partitioned between chloroform (50 mL) and saturated aqueous sodium carbonate (50 mL)
2. customThe layers were separated
3. extractionthe aqueous layer extracted with chloroform (50 mL)
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customto afford an oil
8. stirringThe reaction mixture was stirred at ambient temperature for one hour
9. customThe aqueous layer was separated
10. extractionextracted with chloroform (50 mL)
11. dry with materialThe combined organic fractions were dried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated under reduced pressure
14. customto provide 2.1 g of crude product as a tan solid
15. customThe crude product was purified by column chromatography
16. custommodular high-performance flash purification product available from Biotage, Inc, Charlottesville, Va
17. wash) (eluting with dichloromethane