تفاعل #9587

معادلة التفاعل

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

المردود 35.0%

المذيبات

dichloromethane

ظروف التفاعل

المعالجة

1. 1
   تركيزconcentrated under reduced pressure
2. 2
   workup.ADDITIONEthanol (92 mL) and triethylamine (10.31 mL) were added to the residue
3. 3
   درجة الحرارةthe reaction was heated
4. 4
   درجة الحرارةat reflux temperature for 1.5 hours
5. 5
   أخرىA precipitate formed
6. 6
   تركيزconcentrated under reduced pressure
7. 7
   workup.DISSOLUTIONThe residue was dissolved in dichloromethane
8. 8
   غسيلwashed sequentially with water and saturated aqueous sodium chloride
9. 9
   تجفيفThe organic fraction was dried over magnesium sulfate
10. 10
    ترشيحfiltered
11. 11
    تركيزconcentrated under reduced pressure
12. 12
    أخرىAn initial purification by flash column chromatography
13. 13
    غسيلeluting with a gradient of CMA in chloroform (2–10%)
14. 14
    أخرىwas followed by recrystallization from acetonitrile

الإجراء التجريبي

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.

المصدر