Boron tribromide → N-{3-[4-amino-2-(2-hydroxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}-4-methylbenzenesulfonamide

HRID 1925454Notes

Reaction equation

HRID 1925454 reaction equation
B(Br)(Br)Br.[NH2:5][C:6]1[C:15]2[N:16]=[C:17]([CH2:33][CH2:34][O:35]C)[N:18]([CH2:19][CH2:20][CH2:21][NH:22][S:23]([C:26]3[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=3)(=[O:25])=[O:24])[C:14]=2[C:13]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[N:7]=1>ClCCl.C(#N)C>[NH2:5][C:6]1[C:15]2[N:16]=[C:17]([CH2:33][CH2:34][OH:35])[N:18]([CH2:19][CH2:20][CH2:21][NH:22][S:23]([C:26]3[CH:27]=[CH:28][C:29]([CH3:32])=[CH:30][CH:31]=3)(=[O:25])=[O:24])[C:14]=2[C:13]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[N:7]=1

Participants

5

Reactant 2

HCID 25134Boron tribromideHCID 10072618HCID 10072618, compound

Product 1

HCID 57555837N-{3-[4-amino-2-(2-hydroxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}-4-methylbenzenesulfonamide

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-f1edaba566e84d3da578165319639e31
Source dataset
uspto-grants-2012_05
Patent number
US08178677B2

Reaction notes

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