反应详情

4-Amino-1-(2-hydroxy-2-methylpropyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-7-ol, (2.5 g, 7.5 mmol) was slurried in 75 mL of THF to which 3-pyridylcarbinol (350 mg, 3.18 mmol) and triphenylphosphine (1.59 g, 6.06 mmol) were added. To this was added 1.2 g (5.93 mmol) of diisopropyl azodicarboxylate (DIAD) and the reaction mixture was stirred for 45 minutes. Approximately 3 additional equivalents of each reagent were added to complete the reaction. The reaction mixture was then concentrated and partitioned between chloroform and aqueous sodium carbonate. The organic fraction was dried and passed through an ion exchange resin with methanol, followed by 1M ammonia in methanol as the eluents. The solvent was concentrated and the residue was purified by flash column chromatography on silica gel using a gradient of 0-40% CMA in chloroform. The desired fractions were concentrated to produce an oil which was taken up in 20 mL of refluxing acetonitrile. Upon cooling, white crystals formed which were filtered and dried to provide 0.55 g of 1-[4-amino-2-(2-methoxyethyl)-7-(pyridin-3-ylmethoxy)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol, mp 200.0-202.0° C.

1. additionwere added
2. additionApproximately 3 additional equivalents of each reagent were added
3. customthe reaction
4. concentrationThe reaction mixture was then concentrated
5. custompartitioned between chloroform and aqueous sodium carbonate
6. customThe organic fraction was dried
7. concentrationThe solvent was concentrated
8. customthe residue was purified by flash column chromatography on silica gel using a gradient of 0-40% CMA in chloroform
9. concentrationThe desired fractions were concentrated
10. customto produce an oil which
11. temperatureUpon cooling
12. customwhite crystals formed which
13. filtrationwere filtered
14. customdried