Triethylamine → tert-butyl [4-(7-bromo-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-ylmethyl)benzyl]carbamate

HRID 9491

Reaction equation

HRID 9491 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[NH:12][CH2:13][C:14]1[CH:28]=[CH:27][C:17]([CH2:18][NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:16][CH:15]=1)=[CH:9][CH:8]=[C:7]([Br:29])[CH:6]=2.C(N(CC)CC)C.[CH2:37]([O:39][CH2:40][C:41](Cl)=O)[CH3:38]>ClCCl>[C:22]([O:21][C:20](=[O:26])[NH:19][CH2:18][C:17]1[CH:27]=[CH:28][C:14]([CH2:13][N:12]2[C:11]3[C:10]4[CH:9]=[CH:8][C:7]([Br:29])=[CH:6][C:5]=4[N:4]=[CH:3][C:2]=3[N:1]=[C:38]2[CH2:37][O:39][CH2:40][CH3:41])=[CH:15][CH:16]=1)([CH3:24])([CH3:25])[CH3:23]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 84189Ethoxyacetyl chlorideHCID 21984367Tert-butyl {4-[(3-amino-7-bromoquinolin-4-ylamino)methyl]benzyl}carbamate

Product 1

HCID 86593767tert-butyl [4-(7-bromo-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-ylmethyl)benzyl]carbamateYield 35%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl {4-[(3-amino-7-bromoquinolin-4-ylamino)methyl]benzyl}carbamate (8.46 g, 18.5 mmol), triethylamine (2.25 mL) and dichloromethane (92 mL) were combined. Ethoxyacetyl chloride (2.92 g, 24 mmol) was added dropwise to the mixture. The reaction was stirred for an additional 1.5 hours and then concentrated under reduced pressure. Ethanol (92 mL) and triethylamine (10.31 mL) were added to the residue and the reaction was heated at reflux temperature for 1.5 hours. A precipitate formed. The reaction was cooled to room temperature and then concentrated under reduced pressure. The residue was dissolved in dichloromethane and washed sequentially with water and saturated aqueous sodium chloride. The organic fraction was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. An initial purification by flash column chromatography eluting with a gradient of CMA in chloroform (2–10%) was followed by recrystallization from acetonitrile to provide 3.4 g of tert-butyl[4-(7-bromo-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-ylmethyl)benzyl]carbamate as yellow-orange crystals.

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionEthanol (92 mL) and triethylamine (10.31 mL) were added to the residue
  3. temperaturethe reaction was heated
  4. temperatureat reflux temperature for 1.5 hours
  5. customA precipitate formed
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residue was dissolved in dichloromethane
  8. washwashed sequentially with water and saturated aqueous sodium chloride
  9. dry with materialThe organic fraction was dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customAn initial purification by flash column chromatography
  13. washeluting with a gradient of CMA in chloroform (2–10%)
  14. customwas followed by recrystallization from acetonitrile

Sources & evidence

ORD record
ord-8944d4bc581b4c2091b717fc29f8e6a3
Source dataset
uspto-grants-2006_08
Patent number
US07091214B2

Linked notes

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