反应详情

温度

0 °C

Boron tribromide (5.50 mL of 1 M in dichloromethane) was added dropwise to a chilled (0° C.) suspension of N-{3-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}-4-methylbenzenesulfonamide (1.0 g, 2.2 mmol; U.S. Pat. No. 6,677,349, Example 253) in dichloromethane (20 mL). The reaction mixture was stirred at 0° C. for 3 hours. The reaction mixture was quenched with methanol. Hydrochloric acid (about 10 mL of 6 N) was added and the mixture was stirred at 50° C. overnight. The mixture was diluted with water (50 mL) and ethyl acetate (100 mL) and then brought to neutral pH with solid sodium hydroxide. The layers were separated and the aqueous was extracted with ethyl acetate (×2). The combined organics were dried over magnesium sulfate, filtered, and then concentrated under reduced pressure to provide a yellow solid. This material was purified by prep HPLC (COMBIFLASH system eluting first with a gradient of 0 to 5% methanol in dichloromethane containing 1% ammonium hydroxide and then with a gradient of 5 to 10% methanol in dichloromethane containing 1% ammonium hydroxide) to provide a white solid. This material was suspended in hot acetonitrile, allowed to cool, and then the solvent was decanted. The resulting material was dried under vacuum to provide about 200 mg of N-{3-[4-amino-2-(2-hydroxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}-4-methylbenzenesulfonamide as a white solid, m p. 231-232° C. Anal. calcd for C22H25N5O3S.0.20 CH4O: % C, 59.79; % H, 5.85; % N, 15.70. Found: % C, 59.44; % H, 5.89; % N, 15.52.

1. temperaturea chilled
2. customThe reaction mixture was quenched with methanol
3. additionHydrochloric acid (about 10 mL of 6 N) was added
4. stirringthe mixture was stirred at 50° C. overnight
5. additionThe mixture was diluted with water (50 mL) and ethyl acetate (100 mL)
6. customThe layers were separated
7. extractionthe aqueous was extracted with ethyl acetate (×2)
8. dry with materialThe combined organics were dried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customto provide a yellow solid
12. customThis material was purified by prep HPLC (COMBIFLASH system
13. washeluting first with a gradient of 0 to 5% methanol in dichloromethane containing 1% ammonium hydroxide
14. customwith a gradient of 5 to 10% methanol in dichloromethane containing 1% ammonium hydroxide) to provide a white solid
15. temperatureto cool
16. customthe solvent was decanted
17. customThe resulting material was dried under vacuum