Chloroform → 1-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}cyclobutanol

HRID 1469247Notes

Reaction equation

HRID 1469247 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([OH:18])[CH2:17][CH2:16][CH2:15]1)=[CH:9][CH:8]=[CH:7][CH:6]=2.C(N(CC)CC)C.C(Cl)(Cl)Cl.[CH2:30]([O:32][CH2:33][C:34](Cl)=O)[CH3:31]>ClCCl>[CH2:30]([O:32][CH2:33][C:34]1[N:12]([CH2:13][C:14]2([OH:18])[CH2:17][CH2:16][CH2:15]2)[C:11]2[C:10]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[N:4]=[CH:3][C:2]=2[N:1]=1)[CH3:31]

Participants

6

Reactant 4

HCID 6212ChloroformHCID 8471Triethylamine2×HCID 84189Ethoxyacetyl chloride2×HCID 574578121-{[(3-Aminoquinolin-4-yl)amino]methyl}cyclobutanol

Product 1

HCID 575153931-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}cyclobutanolYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 1-{[(3-aminoquinolin-4-yl)amino]methyl}cyclobutanol (23.1 mmol, prepared as described in Part D) in dichloromethane (154 mL) and triethylamine (3.54 mL, 25.4 mmol) at 0° C. was added chloroform (100 mL). The mixture was allowed to warm to rt and approximately two thirds of the starting material dissolved. To the mixture was slowly added ethoxyacetyl chloride (88%, 3.1 g, 24.3 mmol). The solution was stirred at rt for 2 h. More triethylamine (2 mL) and ethoxyacetyl chloride (88%, 1.0 g) were added. After an additional 16 h, the reaction solution was concentrated in vacuo. To the residue was added ethanol (190 mL) and triethylamine (13 mL). The resulting solution was heated at reflux for 20 h and then concentrated in vacuo to a yellow solid. The solid was partitioned between dichloromethane (400 mL) and water (100 mL). The organic layer was washed with water (100 mL) and brine (100 mL). The organic layer was dried over MgSO4, filtered, and concentrated. The crude product was crystallized from acetonitrile and the crystals were isolated by filtration to provide 1-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}cyclobutanol (4.52 g, 63%).

Workup

  1. dissolutionapproximately two thirds of the starting material dissolved
  2. waitAfter an additional 16 h
  3. concentrationthe reaction solution was concentrated in vacuo
  4. additionTo the residue was added ethanol (190 mL) and triethylamine (13 mL)
  5. temperatureThe resulting solution was heated
  6. temperatureat reflux for 20 h
  7. concentrationconcentrated in vacuo to a yellow solid
  8. customThe solid was partitioned between dichloromethane (400 mL) and water (100 mL)
  9. washThe organic layer was washed with water (100 mL) and brine (100 mL)
  10. dry with materialThe organic layer was dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude product was crystallized from acetonitrile
  14. customthe crystals were isolated by filtration

Sources & evidence

ORD record
ord-cead371457a94066ac95b9292e1e097a
Source dataset
uspto-grants-2015_04
Patent number
US09006264B2

Reaction notes

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