Trifluoroacetic acid → HCID 19605126, compound

Temperature

100 °C

A 25 ml potion of trifluoroacetic acid was added to 1.64 g of 2-(N-t-butoxycarbonylamino)methyl-5-phthalimidomethylthiazole under ice-cooling, and the mixture was then allowed to stand at room temperature for 1 hour. The solvent was evaporated under reduced pressure, and to the resulting residue, 75 ml of dichloromethane and 25 ml of an aqueous saturated sodium bicarbonate solution were added under ice-cooling, followed by stirring. After the aqueous layer was separated, the organic layer was similarly washed once with the aqueous saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate, and then filtered, and the solvent was evaporated under reduced pressure. Afterward, 997 mg of the resulting residue was dissolved in 9 ml of dichloromethane, and a mixed acid anhydride solution comprising a mixed solution of 0.446 ml of acetic anhydride and 0.446 ml of formic acid which had been beforehand reacted with each other at 50° C. for 30 minutes was then added thereto under ice-cooling. After 2 hours, 9 ml of the aqueous saturated sodium bicarbonate solution was added to the reaction solution. The solution was extracted with dichloromethane (9 ml×2). The combined organic layer was washed with the aqueous saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate, and then filtered, and the solvent was evaporated under reduced pressure. Then, to 1.22 g of the resulting residue, 8.9 ml of phosphorus oxychloride was added, followed by stirring under heating at 100° C. for 1 hour. The reaction solution was concentrated under reduced pressure, and the resulting residue was then diluted with 21 ml of dichloromethane under ice-cooling. To this solution, 9 ml of the aqueous saturated sodium bicarbonate solution and 3.2 ml of an aqueous saturated potassium carbonate solution were added under ice-cooling, and after stirring, the organic layer was separated. Furthermore, the aqueous layer was extracted with dichloromethane (27 ml×2). The combined organic layer was washed with the aqueous saturated sodium bicarbonate solution, and the organic layer was dried over anhydrous sodium sulfate, and then filtered. Afterward, the solvent was evaporated under reduced pressure, and the resulting residue was then purified by a silica gel column chromatograph and Cephadex LH-20 in succession to obtain 412 mg of 2-phthalimidomethylimidazo[5,1-b]thiazole.

1. temperaturecooling
2. customThe solvent was evaporated under reduced pressure
3. additionto the resulting residue, 75 ml of dichloromethane and 25 ml of an aqueous saturated sodium bicarbonate solution were added under ice-
4. temperaturecooling
5. customAfter the aqueous layer was separated
6. washthe organic layer was similarly washed once with the aqueous saturated sodium bicarbonate solution
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationfiltered
9. customthe solvent was evaporated under reduced pressure
10. dissolutionAfterward, 997 mg of the resulting residue was dissolved in 9 ml of dichloromethane
11. customhad been beforehand reacted with each other at 50° C. for 30 minutes
12. additionwas then added
13. temperatureunder ice-cooling
14. waitAfter 2 hours
15. extractionThe solution was extracted with dichloromethane (9 ml×2)
16. washThe combined organic layer was washed with the aqueous saturated sodium bicarbonate solution
17. dry with materialdried over anhydrous sodium sulfate
18. filtrationfiltered
19. customthe solvent was evaporated under reduced pressure
20. additionThen, to 1.22 g of the resulting residue, 8.9 ml of phosphorus oxychloride was added
21. stirringby stirring
22. concentrationThe reaction solution was concentrated under reduced pressure
23. additionthe resulting residue was then diluted with 21 ml of dichloromethane under ice-
24. temperaturecooling
25. additionTo this solution, 9 ml of the aqueous saturated sodium bicarbonate solution and 3.2 ml of an aqueous saturated potassium carbonate solution were added under ice-
26. temperaturecooling
27. stirringafter stirring
28. customthe organic layer was separated
29. extractionFurthermore, the aqueous layer was extracted with dichloromethane (27 ml×2)
30. washThe combined organic layer was washed with the aqueous saturated sodium bicarbonate solution
31. dry with materialthe organic layer was dried over anhydrous sodium sulfate
32. filtrationfiltered
33. customAfterward, the solvent was evaporated under reduced pressure
34. customthe resulting residue was then purified by a silica gel column chromatograph and Cephadex LH-20 in succession

ORD record

ord-7c8458b743cd4225b95952ddead5b9fb

Source dataset

uspto-grants-1999_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05990101