Triethylamine → 1-{4-amino-7-[2-(methylsulfonyl)ethenyl]-1H-imidazo[4,5-c]quinolin-1-yl}-2-methylpropan-2-ol

Temperature

120 °C

A thick walled glass tube, equipped with a stir bar, was charged with palladium (II) acetate (15 mg, 0.07 mmol), acetonitrile (50 mL), methyl vinyl sulfone (268 mg, 2.52 mmol), triethylamine (1.00 mL, 7.17 mmol), tri-o-tolylphosphine (45 mg, 0.21 mmol) and 1-(4-amino-7-bromo-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol (800 mg, 2.39 mmol). The reaction mixture was purged with nitrogen and the tube was sealed and heated at 120° C. in an oil bath. The reaction was maintained at 120° C. for 12 hours, cooled to ambient temperature, and then concentrated under reduced pressure to yield a dark brown oil. The oil was partitioned between chloroform (75 mL) and a solution comprised of a 1:1 combination of 10% aqueous potassium carbonate and 10% sodium hydroxide. A precipitate formed. The mixture was filtered and the recovered solid was purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with 20% methanol in dichloromethane. The filtrate was also concentrated and the residue purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with a 0-8% gradient of methanol in dichloromethane). The two lots of purified product were combined to provide 380 mg of 1-{4-amino-7-[2-(methylsulfonyl)ethenyl]-1H-imidazo[4,5-c]quinolin-1-yl}-2-methylpropan-2-ol as a pale yellow solid. MS (APCI) m/z 361 (M+H)+.

1. customA thick walled glass tube, equipped with a stir bar
2. customThe reaction mixture was purged with nitrogen
3. customthe tube was sealed
4. temperatureThe reaction was maintained at 120° C. for 12 hours
5. temperaturecooled to ambient temperature
6. concentrationconcentrated under reduced pressure
7. customto yield a dark brown oil
8. customThe oil was partitioned between chloroform (75 mL)
9. customA precipitate formed
10. filtrationThe mixture was filtered
11. customthe recovered solid was purified by chromatography
12. washeluting with 20% methanol in dichloromethane
13. concentrationThe filtrate was also concentrated
14. customthe residue purified by chromatography
15. washeluting with a 0-8% gradient of methanol in dichloromethane)

ORD record

ord-0dca1592429a492d902a087310199b1d

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658666B2