反応 #9587

反応方程式

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

収率 35.0%

溶媒

dichloromethane

反応条件

後処理

1. 1
   濃縮concentrated under reduced pressure
2. 2
   workup.ADDITIONEthanol (92 mL) and triethylamine (10.31 mL) were added to the residue
3. 3
   温度the reaction was heated
4. 4
   温度at reflux temperature for 1.5 hours
5. 5
   その他A precipitate formed
6. 6
   濃縮concentrated under reduced pressure
7. 7
   workup.DISSOLUTIONThe residue was dissolved in dichloromethane
8. 8
   洗浄washed sequentially with water and saturated aqueous sodium chloride
9. 9
   乾燥The organic fraction was dried over magnesium sulfate
10. 10
    ろ過filtered
11. 11
    濃縮concentrated under reduced pressure
12. 12
    その他An initial purification by flash column chromatography
13. 13
    洗浄eluting with a gradient of CMA in chloroform (2–10%)
14. 14
    その他was followed by recrystallization from acetonitrile

実験手順

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.

出典