Reacción #9525

Ecuación de reacción

Dimethyl 5-(4-amino-7-bromo-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)pentane-1-sulfonamide

pyridine-3-boronic acid

pyridine-3-boronic acid

→

dimethyl 5-[4-amino-2-ethoxymethyl-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-1-yl]pentane-1-sulfonamide

Rendimiento 34.2%

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONwas added
2. 2
   TemperaturaHeating
3. 3
   TemperaturaThe reaction was heated for another 22 hours
4. 4
   OtroThe crude product was purified twice by HPFC (
5. 5
   Lavadoeluting with chloroform
6. 6
   OtroCMA in a gradient from 100:0 to 80:20) and then triturated with ethyl acetate
7. 7
   Otroisolated by filtration
8. 8
   OtroThe product was finally recrystallized from isopropanol
9. 9
   Otroisolated by filtration
10. 10
    Otrodried for eight hours under high vacuum at 100° C.

Procedimiento

Dimethyl 5-(4-amino-7-bromo-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)pentane-1-sulfonamide (0.26 g, 0.53 mmol) and pyridine-3-boronic acid (0.78 g, 0.63 mmol) were coupled according to the method described in Part J of Example 1. The reaction was heated at 100° C. for 31 hours, at which time additional palladium acetate (0.002 equivalent) was added. Heating was resumed for 14 hours, and then additional pyridine-3-boronic acid (0.3 equivalent) was added. The reaction was heated for another 22 hours. The work-up procedure used in Part F of Examples 125–135 was followed. The crude product was purified twice by HPFC (eluting with chloroform:CMA in a gradient from 100:0 to 80:20) and then triturated with ethyl acetate and isolated by filtration. The product was finally recrystallized from isopropanol, isolated by filtration, and dried for eight hours under high vacuum at 100° C. to provide 0.090 g of dimethyl 5-[4-amino-2-ethoxymethyl-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-1-yl]pentane-1-sulfonamide as a white powder, mp 159–160° C.

Fuente