Reaktion #9587

Reaktionsgleichung

tert-Butyl {4-[(3-amino-7-bromoquinolin-4-ylamino)methyl]benzyl}carbamate

triethylamine

Ethoxyacetyl chloride

→

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

Ausbeute 35.0%

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Einengenconcentrated under reduced pressure
2. 2
   workup.ADDITIONEthanol (92 mL) and triethylamine (10.31 mL) were added to the residue
3. 3
   Temperaturthe reaction was heated
4. 4
   Temperaturat reflux temperature for 1.5 hours
5. 5
   SonstigeA precipitate formed
6. 6
   Einengenconcentrated under reduced pressure
7. 7
   workup.DISSOLUTIONThe residue was dissolved in dichloromethane
8. 8
   Waschenwashed sequentially with water and saturated aqueous sodium chloride
9. 9
   TrocknenThe organic fraction was dried over magnesium sulfate
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated under reduced pressure
12. 12
    SonstigeAn initial purification by flash column chromatography
13. 13
    Wascheneluting with a gradient of CMA in chloroform (2–10%)
14. 14
    Sonstigewas followed by recrystallization from acetonitrile

Vorschrift

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.

Quelle