Acetonitrile → Azacytidine

HRID 1510805Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1510805
C[Si]([NH:5][C:6]1[N:11]=[C:10]([O:12][Si](C)(C)C)[N:9]=[CH:8][N:7]=1)(C)C.C(O[C@@H:21]1[O:43][C@H:42]([CH2:44][O:45]C(=O)C2C=CC=CC=2)[C@@H:32]([O:33]C(=O)C2C=CC=CC=2)[C@H:22]1[O:23]C(=O)C1C=CC=CC=1)(=O)C.CC#N.S(O)(C(F)(F)F)(=O)=O>CS(C)=O>[CH:8]1[N:9]([C@@H:21]2[O:43][C@H:42]([CH2:44][OH:45])[C@@H:32]([OH:33])[C@H:22]2[OH:23])[C:10](=[O:12])[N:11]=[C:6]([NH2:5])[N:7]=1

Komponenten

6

Edukt 4

HCID 6342AcetonitrileHCID 62406Trifluoromethanesulfonic acidHCID 81455beta-D-Ribofuranose, 1-acetate 2,3,5-tribenzoateHCID 529002N-(Trimethylsilyl)-4-((trimethylsilyl)oxy)-1,3,5-triazin-2-amine

Produkt 1

HCID 9444AzacytidineAusbeute 71 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 679Dimethyl SulfoxideLösungsmittel

Reaktionsbedingungen

Temperatur
55 °C

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-85e30dad575045c4889ee1c3acc9c85c
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08212021B2

Notizen zur Reaktion

Wird geladen…