Reacción #73006

Ecuación de reacción

p-toluenesulfonyl chloride

ammonium hydroxide

1-{3-[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}cyclohexanol

m-CPBA

→

1-{3-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}cyclohexanol

Rendimiento 53.0%

Disolventes

chloroform

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGThe mixture was stirred at 0° C. for 1 h
2. 2
   Filtraciónwas filtered
3. 3
   workup.ADDITIONThe filtrate was diluted with dichloromethane (30 mL) and saturated aqueous sodium bicarbonate (30 mL)
4. 4
   OtroThe layers were separated
5. 5
   Extracciónthe aqueous layer was extracted with dichloromethane (20 mL)
6. 6
   Secadodried over MgSO4
7. 7
   Filtraciónfiltered
8. 8
   Concentraciónconcentrated
9. 9
   Otroto afford an orange solid, which
10. 10
    Otrowas purified by HPFC (silica gel, eluted with 0-35% CMA/chloroform)
11. 11
    ConcentraciónThe appropriate fractions were concentrated
12. 12
    Otroto afford a tan solid
13. 13
    Otrothat was crystallized from chloroform/hexanes
14. 14
    Otrodried at 75° C. under vacuum

Procedimiento

To a solution of 1-{3-[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}cyclohexanol (1.10 g, 2.99 mmol) in chloroform (15 mL) at rt was added m-CPBA (0.96 g, 3.89 mmol) in portions. The reaction was stirred for 1.5 h, then was cooled to 0° C. and concentrated ammonium hydroxide (5 mL) was added followed by portionwise addition of p-toluenesulfonyl chloride (0.630 g, 3.29 mmol). The mixture was stirred at 0° C. for 1 h, then was filtered. The filtrate was diluted with dichloromethane (30 mL) and saturated aqueous sodium bicarbonate (30 mL). The layers were separated and the aqueous layer was extracted with dichloromethane (20 mL). The organic layers were combined, dried over MgSO4, filtered, and concentrated to afford an orange solid, which was purified by HPFC (silica gel, eluted with 0-35% CMA/chloroform). The appropriate fractions were concentrated to afford a tan solid that was crystallized from chloroform/hexanes and dried at 75° C. under vacuum to afford 1-{3-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}cyclohexanol as white crystals (600 mg, 53%), mp 175-176° C. Anal. calcd for C22H30N4O2: C, 69.08; H, 7.91; N, 14.65.

Fuente