Reacción #1274599

Ecuación de reacción

acetone O-[3-(4-amino-7-bromo-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]oxime

phenylboronic acid

sodium carbonate

n-propanol

→

acetone O-[3-(4-amino-7-phenyl-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]oxime

Rendimiento 55.8%

Disolventes

Chloroform

toluene

water

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONback-filled with nitrogen three times
2. 2
   OtroThe pressure vessel was sealed
3. 3
   Temperaturato cool to ambient temperature
4. 4
   Lavadothe mixture was washed with water (2×10 mL) and brine (10 mL)
5. 5
   Secadodried over sodium sulfate
6. 6
   Filtraciónfiltered
7. 7
   Concentraciónconcentrated under reduced pressure
8. 8
   OtroThe product was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 0-35% CMA in chloroform)
9. 9
   Otroto yield a solid
10. 10
    Otrothat was triturated twice with acetonitrile
11. 11
    Otroisolated

Procedimiento

In a pressure vessel under a nitrogen atmosphere, acetone O-[3-(4-amino-7-bromo-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]oxime (500 mg, 1.20 mmol), phenylboronic acid (219 mg, 1.80 mmol), a solution of palladium (II) acetate (2.7 mg, 0.012 mmol) in hot toluene (0.5 mL), triphenylphosphine (9.5 mg, 0.036 mmol), and 2 M aqueous sodium carbonate (0.72 mL, 1.44 mmol) were combined in 5:1 n-propanol:water (2.4 mL). The solution was placed under vacuum and back-filled with nitrogen three times. The pressure vessel was sealed and heated at 100° C. overnight, then was allowed to cool to ambient temperature. Chloroform (60 mL) was added and the mixture was washed with water (2×10 mL) and brine (10 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The product was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 0-35% CMA in chloroform) to yield a solid that was triturated twice with acetonitrile and isolated to yield 278 mg of acetone O-[3-(4-amino-7-phenyl-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]oxime as a white powder, mp 164.0-165.0° C.

Fuente