Réaction #9589

Équation de réaction

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

pyridine-3-boronic acid 1,3-propanediol cyclic ester

sodium carbonate

n-propanol

→

tert-butyl{4-[4-amino-2-ethoxymethyl-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-1-ylmethyl]benzyl}carbamate

Rendement 64.1%

Solvants

water

Conditions de réaction

Traitement

1. 1
   Autrethe flask was flushed with nitrogen
2. 2
   workup.ADDITIONPalladium(II) acetate (0.0013 g) in toluene (0.200 mL) was added
3. 3
   Autrethe flask was again flushed with nitrogen
4. 4
   AutreThe flask was sealed
5. 5
   Températureto cool to room temperature
6. 6
   workup.ADDITIONthe mixture was diluted with dichloromethane and water
7. 7
   AutreThe layers were separated
8. 8
   Extractionthe aqueous fraction was extracted with dichloromethane
9. 9
   Lavagewashed sequentially with water and saturated aqueous sodium chloride
10. 10
    Séchagedried over sodium sulfate
11. 11
    Filtrationfiltered
12. 12
    Concentrationconcentrated under reduced pressure
13. 13
    AutrePurification of the residue by flash column chromatography
14. 14
    Lavageeluting with a gradient of CMA/chloroform and subsequent recrystallization from acetonitrile

Mode opératoire

tert-Butyl[4-(4-amino-7-bromo-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-ylmethyl)benzyl]carbamate (1.15 g, 2.1 mmol), triphenylphosphine (0.005 g), pyridine-3-boronic acid 1,3-propanediol cyclic ester (0.365 g, 2.2 mmol), and n-propanol (3.67 mL) were combined. Aqueous sodium carbonate (2M, 1.12 mL) and water (0.6 mL) were added to the mixture and the flask was flushed with nitrogen. Palladium(II) acetate (0.0013 g) in toluene (0.200 mL) was added, and the flask was again flushed with nitrogen. The flask was sealed and heated in an oil bath at a temperature of 105° C. for 16 hours. The reaction was allowed to cool to room temperature and the mixture was diluted with dichloromethane and water. The layers were separated and the aqueous fraction was extracted with dichloromethane. The organic fractions were combined, washed sequentially with water and saturated aqueous sodium chloride, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the residue by flash column chromatography eluting with a gradient of CMA/chloroform and subsequent recrystallization from acetonitrile yielded 0.725 g of tert-butyl{4-[4-amino-2-ethoxymethyl-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-1-ylmethyl]benzyl}carbamate as flocculent white crystals, m.p. 195.5–197.0° C.

Source