반응 #9587

반응 방정식

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

수율 35.0%

용매

dichloromethane

반응 조건

후처리

1. 1
   농축concentrated under reduced pressure
2. 2
   workup.ADDITIONEthanol (92 mL) and triethylamine (10.31 mL) were added to the residue
3. 3
   온도the reaction was heated
4. 4
   온도at reflux temperature for 1.5 hours
5. 5
   기타A precipitate formed
6. 6
   농축concentrated under reduced pressure
7. 7
   workup.DISSOLUTIONThe residue was dissolved in dichloromethane
8. 8
   세척washed sequentially with water and saturated aqueous sodium chloride
9. 9
   건조The organic fraction was dried over magnesium sulfate
10. 10
    여과filtered
11. 11
    농축concentrated under reduced pressure
12. 12
    기타An initial purification by flash column chromatography
13. 13
    세척eluting with a gradient of CMA in chloroform (2–10%)
14. 14
    기타was followed by recrystallization from acetonitrile

실험 절차

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.

출처