Dichloromethane → 1-(4-amino-7-bromo-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol

HRID 244828Notes

Reaction equation

HRID 244828 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:14]([CH2:15][C:16]([CH3:19])([OH:18])[CH3:17])[CH:13]=[N:12][C:7]=3[CH:8]=[N:9][C:10]=2[CH:11]=1.ClCCl.[OH-].[NH4+:24].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C(Cl)(Cl)Cl>[NH2:24][C:8]1[C:7]2[N:12]=[CH:13][N:14]([CH2:15][C:16]([CH3:19])([OH:18])[CH3:17])[C:6]=2[C:5]2[CH:4]=[CH:3][C:2]([Br:1])=[CH:11][C:10]=2[N:9]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 73974-Toluenesulfonyl chlorideHCID 14923Ammonium HydroxideHCID 690804421-(7-bromo-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol

Product 1

HCID 690807241-(4-amino-7-bromo-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A 1-liter round bottom flask was charged with 1-(7-bromo-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol (25.0 g, 78.0 mmol), dichloromethane (400 mL) and chloroform (100 mL). To this solution was slowly added in small portions 3-chloroperoxybenxzoic acid (34.0 g of 60% purity, 117 mmol, 1.5 eq). The reaction was maintained at room temperature for 2 hours and then concentrated ammonium hydroxide solution (200 mL) was added. The mixture was vigorously stirred as p-toluenesulfonyl chloride (22.4 g, 117 mmol) was slowly added in small portions. The reaction was complete within 1 hour but was left to stir at room temperature overnight. The reaction mixture was filtered to collect a pale yellow solid. The product was purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with 0-30% CMA in chloroform). The resulting pale yellow solid was slurried in cold acetonitrile, isolated by filtration, and air-dried on the vacuum filter to provide 17.2 g of 1-(4-amino-7-bromo-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol. The filtrate was transferred to a separatory funnel and the layers were separated. The aqueous layer was extracted with chloroform (3×100 mL). The chloroform fractions were combined, washed with brine (100 mL), dried over magnesium sulfate and concentrated to dryness to provide an additional 0.8 g of 1-(4-amino-7-bromo-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol, mp>250° C.

Workup

  1. additionTo this solution was slowly added in small portions 3-chloroperoxybenxzoic acid (34.0 g of 60% purity, 117 mmol, 1.5 eq)
  2. additionwas slowly added in small portions
  3. waitwas left
  4. filtrationThe reaction mixture was filtered
  5. customto collect a pale yellow solid
  6. customThe product was purified by chromatography
  7. washa HORIZON HPFC system (silica cartridge, eluting with 0-30% CMA in chloroform)
  8. customisolated by filtration
  9. customair-dried on the vacuum
  10. filtrationfilter

Sources & evidence

ORD record
ord-4e1fa1ac35204a16a549e6fc4e0d0bc8
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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