Реакция #9587

Уравнение реакции

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

Выход 35.0%

Растворители

dichloromethane

Условия реакции

Обработка

1. 1
   Концентрированиеconcentrated under reduced pressure
2. 2
   workup.ADDITIONEthanol (92 mL) and triethylamine (10.31 mL) were added to the residue
3. 3
   Температураthe reaction was heated
4. 4
   Температураat reflux temperature for 1.5 hours
5. 5
   ДругоеA precipitate formed
6. 6
   Концентрированиеconcentrated under reduced pressure
7. 7
   workup.DISSOLUTIONThe residue was dissolved in dichloromethane
8. 8
   Промывкаwashed sequentially with water and saturated aqueous sodium chloride
9. 9
   СушкаThe organic fraction was dried over magnesium sulfate
10. 10
    Фильтрацияfiltered
11. 11
    Концентрированиеconcentrated under reduced pressure
12. 12
    ДругоеAn initial purification by flash column chromatography
13. 13
    Промывкаeluting with a gradient of CMA in chloroform (2–10%)
14. 14
    Другоеwas followed by recrystallization from acetonitrile

Методика

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.

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