反应详情

Ethoxyacetyl chloride (1.82 mL, 16.60 mmol) was added to a chilled (0° C.) solution of tert-butyl [2-(3-amino-7-benzyloxyquinolin-4-ylamino)-1,1-dimethylethyl]carbamate (6.04 g, 13.8 mmol) and triethylamine (3.86 mL, 27.68 mmol) in 150 mL of anhydrous dichloromethane. After stirring for 30 minutes, the cooling bath was removed and the reaction was stirred for 24 hours at ambient temperature. The volatiles were removed under reduced pressure and the resulting residue was dissolved in ethanol, followed by the addition of 3.86 mL of trietylamine. The reaction was heated at reflux for 2.5 days and then cooled to ambient temperature. The solvent was removed under reduced pressure and dichloromethane was added. The solution was sequentially washed with aqueous sodium bicarbonate followed by brine; dried over sodium sulfate; filtered; and concentrated under reduced pressure. The residue was purified using flash column chromatography on silica gel, eluting with 5% methanol in dichloromethane. Clean fractions were concentrated; while fractions containing both the product and the starting material were resubmitted to the reaction conditions and repurified as described above. The combined lots provided a total of 5.07 g of tert-butyl [2-(7-benzyloxy-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)-1,1-dimethylethyl]carbamate was obtained as an orange foam.

1. customthe cooling bath was removed
2. stirringthe reaction was stirred for 24 hours at ambient temperature
3. customThe volatiles were removed under reduced pressure
4. dissolutionthe resulting residue was dissolved in ethanol
5. additionfollowed by the addition of 3.86 mL of trietylamine
6. temperatureThe reaction was heated
7. temperatureat reflux for 2.5 days
8. customThe solvent was removed under reduced pressure and dichloromethane
9. additionwas added
10. washThe solution was sequentially washed with aqueous sodium bicarbonate
11. dry with materialdried over sodium sulfate
12. filtrationfiltered
13. concentrationand concentrated under reduced pressure
14. customThe residue was purified
15. washeluting with 5% methanol in dichloromethane
16. concentrationwere concentrated
17. additionwhile fractions containing both the product
18. customthe starting material were resubmitted to the reaction conditions
19. customrepurified