反应详情

温度

55 °C

A mixture of 2-[(trimethylsilyl)amino]-4-[(trimethylsilyl)oxy]-s-triazine (4.5 Kg), 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose (8.8 Kg), anhydrous MeCN (34.6 Kg) and TfOH (600 g) were heated at 55° C. for 12.5 hours. The reaction mixture was cooled to 45° C., DMSO (29 Kg) was added, and the MeCN was evaporated at an internal temperature of <50° C. under vacuum until about 54 L of the solution. The solution was cooled to 23° C. MeOH (13.9 Kg) was added followed by a solution of 30% NaOMe in MeOH solution (2.5 Kg) that was pre-diluted with MeOH (7.0 Kg). The solution was stirred at 23° C. for 35 minutes. When the reaction was complete MeOH (90.4 Kg) was added and the resulting slurry was stirred at 22° C. for 3 hours and 10 minutes and was then filtered and washed three times with MeOH (7.0 Kg each). The cake was dried under vacuum at below 70° C. for 9 hours and 20 minutes to give 3.2 Kg of 98.89% purity crude azacitidine (71% yield based on 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose).

1. temperatureThe reaction mixture was cooled to 45° C.
2. customthe MeCN was evaporated at an internal temperature of <50° C. under vacuum until about 54 L of the solution
3. temperatureThe solution was cooled to 23° C
4. additionMeOH (13.9 Kg) was added
5. additionwas pre-diluted with MeOH (7.0 Kg)
6. additionwas added
7. stirringthe resulting slurry was stirred at 22° C. for 3 hours and 10 minutes
8. filtrationwas then filtered
9. washwashed three times with MeOH (7.0 Kg each)
10. customThe cake was dried under vacuum at below 70° C. for 9 hours and 20 minutes