反应详情

To a solution of 100 mg (0.59 mmol) of the above-obtained 5-(N-methylamino)methylimidazo[5,1-b]thiazole in 3 ml of methylene chloride was added a mixture which had been prepared in advance by reacting 1 ml of formic acid with 0.2 ml of acetic anhydride at 50° C. for 10 minutes. The mixture was stirred at room temperature for one hour, and then refluxed for 3 hours. To this was added a mixture which had been prepared in advance by reacting 5 ml of formic acid with 2 ml of acetic anhydride at 50° C. for 10 minutes, and the mixture was refluxed for an additional 2 hours. To the reaction solution cooled to room temperature was added 3 ml of toluene, and the mixture was concentrated to dryness under reduced pressure. To the residue were added methylene chloride and a 50% aqueous solution of potassium carbonate, and the mixture was stirred for 10 minutes. The organic layer was separated, and the aqueous layer was extracted three times with methylene chloride. The combined organic layers were dried over anhydrous potassium carbonate, concentrated under reduced pressure, and purified by flash column chromatography using silica gel, eluting with a 9:1 mixture of ethyl acetate and methanol to give 89 mg (yield 77%) of the title compound as colorless crystals.

1. customhad been prepared in advance
2. customat 50° C.
3. customfor 10 minutes
4. temperaturerefluxed for 3 hours
5. additionTo this was added a mixture which
6. customhad been prepared in advance
7. customat 50° C.
8. customfor 10 minutes
9. temperaturethe mixture was refluxed for an additional 2 hours
10. temperatureTo the reaction solution cooled to room temperature
11. concentrationthe mixture was concentrated to dryness under reduced pressure
12. additionTo the residue were added methylene chloride
13. stirringa 50% aqueous solution of potassium carbonate, and the mixture was stirred for 10 minutes
14. customThe organic layer was separated
15. extractionthe aqueous layer was extracted three times with methylene chloride
16. dry with materialThe combined organic layers were dried over anhydrous potassium carbonate
17. concentrationconcentrated under reduced pressure
18. custompurified by flash column chromatography
19. washeluting with a 9:1 mixture of ethyl acetate and methanol