Reaction #9589

Reaction equation

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

Yield 64.1%

Solvents

water

Conditions

Workup

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

Procedure

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