Dichloromethane → 1-[8-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol

HRID 244862Notes

Reaction equation

HRID 244862 reaction equation
[CH2:1]([O:3][CH2:4][C:5](Cl)=O)[CH3:2].[NH2:8][C:9]1[CH:10]=[N:11][C:12]2[C:17]([C:18]=1[NH:19][CH2:20][C:21]([CH3:24])([OH:23])[CH3:22])=[CH:16][C:15]([Br:25])=[CH:14][CH:13]=2.ClCCl.C(N(CC)CC)C>O>[Br:25][C:15]1[CH:14]=[CH:13][C:12]2[N:11]=[CH:10][C:9]3[N:8]=[C:5]([CH2:4][O:3][CH2:1][CH3:2])[N:19]([CH2:20][C:21]([CH3:24])([OH:23])[CH3:22])[C:18]=3[C:17]=2[CH:16]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 84189Ethoxyacetyl chlorideHCID 21984278HCID 21984278, compound

Product 1

HCID 690812241-[8-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Ethoxyacetyl chloride (6.2 g, 50.5 mmol) was added dropwise to a solution of crude 1-[(3-amino-6-bromoquinolin-4-yl)amino]-2-methylpropan-2-ol, dichloromethane (500 mL), and triethylamine (7 mL, 50.5 mmol). After stirring for 16 hours, water was added and the mixture was stirred for an additional 2 hours. The fractions were separated. The organic fraction was washed with water, concentrated under reduced pressure and redissolved in ethanol (500 mL). Water (150 mL) and potassium carbonate (10.5 g) were added and the mixture was heated at reflux temperature for 3 hours. The ethanol was removed under reduced pressure. The remaining aqueous fraction was extracted with ethyl acetate (2×500 mL). The organic fractions were combined, washed with water followed by saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. Recrystallization from acetonitrile provided 10.4 g of 1-[8-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol as a tan powder.

Workup

  1. stirringthe mixture was stirred for an additional 2 hours
  2. customThe fractions were separated
  3. washThe organic fraction was washed with water
  4. concentrationconcentrated under reduced pressure
  5. dissolutionredissolved in ethanol (500 mL)
  6. additionWater (150 mL) and potassium carbonate (10.5 g) were added
  7. temperaturethe mixture was heated
  8. temperatureat reflux temperature for 3 hours
  9. customThe ethanol was removed under reduced pressure
  10. extractionThe remaining aqueous fraction was extracted with ethyl acetate (2×500 mL)
  11. washwashed with water
  12. dry with materialdried over anhydrous sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customRecrystallization from acetonitrile

Sources & evidence

ORD record
ord-43a46737ac7e4e5b8c4991302b0f324d
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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