Methane → HCID 10296765, compound

HRID 432838Notes

Reaction equation

HRID 432838 reaction equation
[CH2:1]([C:5]1[N:6]([CH2:23][CH2:24][CH2:25][CH2:26]Cl)[C:7]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:10]=[C:9]([N:17]=CN(C)C)[C:8]=2[N:22]=1)[CH2:2][CH2:3][CH3:4].C(C1N(CCCCCl)C2C3C=CC=CC=3N=C(N)C=2N=1)CCC.[Na+].[C:52]1([S:58]([O-:60])=[O:59])[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1.Cl.O1CCOCC1.C>CO.C(OCC)(=O)C.CN(C)C=O>[CH2:1]([C:5]1[N:6]([CH2:23][CH2:24][CH2:25][CH2:26][S:58]([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)(=[O:60])=[O:59])[C:7]2[C:16]3[CH:11]=[CH:12][CH:13]=[CH:14][C:15]=3[N:17]=[C:9]([NH2:10])[C:8]=2[N:22]=1)[CH2:2][CH2:3][CH3:4]

Participants

10

Reactant 6

HCID 297MethaneHCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 2723840Benzenesulfinic acid, sodium saltHCID 22320426HCID 22320426, compoundHCID 22320461HCID 22320461, compound

Product 1

HCID 10296765HCID 10296765, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A round bottom flask was charged with a magnetic stir bar, a 2:1 mixture of N′-[2-butyl-1-(4-chlorobutyl)-1H-imidazo[4,5-c]quinolin-4-yl]-N,N-dimethylimidoformamide and 2-butyl-1-(4-chlorobutyl)-1H-imidazo[4,5-c]quinolin-4-amine (1.3 g), benzenesulfinic acid sodium salt (1.67 g, 10.11 mmol), and anhydrous dimethyl formamide (15 mL) under a nitrogen atmosphere. The resulting solution was heated to 100° C. to give a homogeneous solution that was maintained at 100° C. for 90 hours at which time the starting materials were completely consumed. The solution was cooled and then partitioned between chloroform and water. The layers were separated. The organic layer was washed with saturated aqueous sodium bicarbonate and brine, dried over anhydrous sodium sulfate, filtered and then concentrated under reduced pressure to afford a dark yellow gum. The material was dissolved in methanol (20 mL) and a 4 M solution of hydrochloric acid in dioxane (3.02 mL, 12.1 mmol). The light orange solution was stirred at ambient temperature for 12 hours at which time the reaction was judged to be complete. The volatiles were removed under reduced pressure to give a light yellow gum. The material was partitioned between chloroform and saturated aqueous sodium bicarbonate. The layers were separated and the aqueous layer was extracted with chloroform (1×). The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate, filtered and then concentrated under reduced pressure to afford a light yellow solid. The material was purified by chromatography over silica gel (95/5 dichloromethane/methanol) to give an off-white solid. The solid (0.63 g) was dissolved in ethyl acetate (50 mL) and brought to reflux. Activated charcoal (0.6 g) was added and the resulting mixture was heated at reflux for 5 minutes. The charcoal was removed by filtration through fluted paper to provide a colorless solution. The solution was concentrated under reduced pressure to give a solid that was recrystallized from ethyl acetate and hexanes to provide 2-butyl-1-[4-(phenylsulfonyl)butyl]-1H-imidazo[4,5-c]quinolin-4-amine (0.37 g, 0.85 mmol) as a white fluffy solid, m.p. 179-180° C. Analysis. Calculated for C24H28N4O2S: % C 66.03; % H, 6.46; % N, 12.83. Found % C 65.88; % H, 6.49; % N, 12.76

Workup

  1. additionA round bottom flask was charged with a magnetic stir bar
  2. customto give a homogeneous solution that
  3. temperaturewas maintained at 100° C. for 90 hours at which time the starting materials
  4. customwere completely consumed
  5. temperatureThe solution was cooled
  6. custompartitioned between chloroform and water
  7. customThe layers were separated
  8. washThe organic layer was washed with saturated aqueous sodium bicarbonate and brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customto afford a dark yellow gum
  13. customThe volatiles were removed under reduced pressure
  14. customto give a light yellow gum
  15. customThe material was partitioned between chloroform and saturated aqueous sodium bicarbonate
  16. customThe layers were separated
  17. extractionthe aqueous layer was extracted with chloroform (1×)
  18. washwashed with brine
  19. dry with materialdried over anhydrous sodium sulfate
  20. filtrationfiltered
  21. concentrationconcentrated under reduced pressure
  22. customto afford a light yellow solid
  23. customThe material was purified by chromatography over silica gel (95/5 dichloromethane/methanol)
  24. customto give an off-white solid
  25. temperatureto reflux
  26. temperaturethe resulting mixture was heated
  27. temperatureat reflux for 5 minutes
  28. customThe charcoal was removed by filtration
  29. customto provide a colorless solution
  30. concentrationThe solution was concentrated under reduced pressure
  31. customto give a solid
  32. customthat was recrystallized from ethyl acetate and hexanes

Sources & evidence

ORD record
ord-aa515329e0264438ad065fe9be2ccc9e
Source dataset
uspto-grants-2003_12
Patent number
US06664264B2

Reaction notes

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