Reaktion #9521

Reaktionsgleichung

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

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

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

triphenylphosphine

→

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

Ausbeute 97.9%

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction was heated
2. 2
   workup.ADDITIONwere added
3. 3
   Temperaturthe reaction was heated for an additional three hours
4. 4
   SonstigeThe crude product was purified twice by column chromatography on silica gel (
5. 5
   Wascheneluting with chloroform
6. 6
   SonstigeCMA in a gradient from 95:5 to 70:30) and then triturated with methanol
7. 7
   Sonstigeisolated by filtration
8. 8
   Sonstigedried for eight hours under high vacuum at 100° C.

Vorschrift

Methyl 4-(4-amino-7-bromo-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)butane-1-sulfonamide (0.78 g, 1.7 mmol) and pyridine-3-boronic acid 1,3-propanediol cyclic ester (0.33 g, 2.0 mmol) were coupled according to the method described in Part J of Example 1. The reaction was heated at reflux for 15 hours, at which time additional pyridine-3-boronic acid 1,3-propanediol cyclic ester, palladium acetate, and triphenylphosphine were added, and the reaction was heated for an additional three hours. The work-up procedure used in Part F of Examples 125–135 was followed. The crude product was purified twice by column chromatography on silica gel (eluting with chloroform:CMA in a gradient from 95:5 to 70:30) and then triturated with methanol, isolated by filtration, and dried for eight hours under high vacuum at 100° C. to provide 0.78 g of methyl 4-[4-amino-2-ethoxymethyl-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-1-yl]butane-1-sulfonamide as off-white needles, mp 216–218° C.

Quelle