Ammonia → 3-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)-2,2-dimethylpropanamide

HRID 2366726Notes

Reaction equation

HRID 2366726 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[CH:13][N:14]([CH2:15][C:16]([CH3:22])([CH3:21])[C:17]([O:19]C)=O)[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1.[OH-].[K+].C(Cl)(=O)C(Cl)=O.[NH3:31].C(=O)(O)[O-].[Na+].Cl>ClCCl.CN(C=O)C.CO.O>[NH2:1][C:2]1[C:11]2[N:12]=[CH:13][N:14]([CH2:15][C:16]([CH3:21])([CH3:22])[C:17]([NH2:31])=[O:19])[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1

Participants

11

Reactant 6

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 65578Oxalyl chloride2×HCID 516892Sodium BicarbonateHCID 69506712HCID 69506712, compound

Product 1

HCID 589703803-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)-2,2-dimethylpropanamide

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A modification of the methods described in Part C of Example 61 was used to treat methyl 3-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)-2,2-dimethylpropanoate (1.61 g, 5.4 mmol) with potassium hydroxide (22 mL of 0.5 M); the reaction was heated at reflux overnight. The reaction with oxalyl chloride (0.96 mL) in dichloromethane (55 mL total) was stirred for one hour before more oxalyl chloride (1.0 mL) and DMF (three drops) were added, and then the reaction was stirred overnight. The precipitate isolated after the reaction with ammonia and treatment with sodium bicarbonate was combined with material from another run and recrystallized from methanol/water. The resulting solid was isolated by filtration and heated gently in a mixture of methanol (35 mL), water (10 mL), and concentrated hydrochloric acid (0.83 mL). The mixture was filtered to remove a small amount of insoluble material, and a precipitate formed in the filtrate. The precipitate was isolated by filtration, recrystallized twice from methanol/water, dried overnight in a vacuum oven at 70° C., and recrystallized four times from ethyl acetate/methanol/water with a filtration through a 20 micron filter prior to the last two crystallizations. The resulting crystals were dried overnight in a vacuum oven at 70° C. to provide 3-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)-2,2-dimethylpropanamide as white crystals, mp 287-289° C.

Workup

  1. temperaturethe reaction was heated
  2. temperatureat reflux overnight
  3. additionwere added
  4. customThe precipitate isolated
  5. customrecrystallized from methanol/water
  6. customThe resulting solid was isolated by filtration
  7. filtrationThe mixture was filtered
  8. customto remove a small amount of insoluble material
  9. customa precipitate formed in the filtrate
  10. customThe precipitate was isolated by filtration
  11. customrecrystallized twice from methanol/water
  12. customdried overnight in a vacuum oven at 70° C.
  13. customrecrystallized four times from ethyl acetate/methanol/water
  14. filtrationwith a filtration through a 20 micron
  15. filtrationfilter
  16. customto the last two crystallizations
  17. customThe resulting crystals were dried overnight in a vacuum oven at 70° C.

Sources & evidence

ORD record
ord-163364d802a043b5ba0a49628cd390e4
Source dataset
uspto-grants-2014_04
Patent number
US08697873B2

Reaction notes

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