Benzenesulfonyl chloride → methyl [4-amino-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-2-yl]carbamate

HRID 1097610Notes

Reaction equation

HRID 1097610 reaction equation
[OH:1][C:2]([CH3:24])([CH3:23])[CH2:3][N:4]1[C:16]2[C:15]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N+:9]([O-])=[CH:8][C:7]=2[N:6]=[C:5]1[NH:18][C:19](=[O:22])[O:20][CH3:21].[OH-].[NH4+:26].C1(S(Cl)(=O)=O)C=CC=CC=1>CO>[NH2:26][C:8]1[C:7]2[N:6]=[C:5]([NH:18][C:19](=[O:22])[O:20][CH3:21])[N:4]([CH2:3][C:2]([OH:1])([CH3:24])[CH3:23])[C:16]=2[C:15]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[N:9]=1

Participants

5

Reactant 3

HCID 7369Benzenesulfonyl chloride2×HCID 14923Ammonium HydroxideHCID 86626309methyl [1-(2-hydroxy-2-methylpropyl)-5-oxido-1H-imidazo[4,5-c]quinolin-2-yl]carbamate

Product 1

HCID 57550537methyl [4-amino-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-2-yl]carbamateYield 45.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of methyl [1-(2-hydroxy-2-methylpropyl)-5-oxido-1H-imidazo[4,5-c]quinolin-2-yl]carbamate (0.80 g, 2.4 mmol) in methanol (10 mL) was stirred vigorously and cooled to 0° C. Concentrated ammonium hydroxide (0.8 mL, 25 mmol) was added followed by benzenesulfonyl chloride (0.9 g, 5 mmol), which was added dropwise. The mixture was stirred for two hours at 0° C. to 5° C. An analysis by LC/MS indicated the reaction was incomplete. Additional benzenesulfonyl chloride (0.9 g) was added, and the reaction mixture was stirred overnight at room temperature. The solvent was removed under reduced pressure, and the residue was purified by automated flash chromatography (40+M silica cartridge, eluting with 0% to 25% CMA in chloroform) followed by recrystallization from ethyl acetate to provide 0.36 g of methyl [4-amino-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-2-yl]carbamate as a white solid, mp 255-258° C. (decomposition).

Workup

  1. additionwas added dropwise
  2. stirringThe mixture was stirred for two hours at 0° C. to 5° C
  3. stirringthe reaction mixture was stirred overnight at room temperature
  4. customThe solvent was removed under reduced pressure
  5. customthe residue was purified by automated flash chromatography (40+M silica cartridge, eluting with 0% to 25% CMA in chloroform)
  6. customfollowed by recrystallization from ethyl acetate

Sources & evidence

ORD record
ord-e5d65f421c004249bd3844edb1cfded0
Source dataset
uspto-grants-2012_03
Patent number
US08143270B2

Reaction notes

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