Phosphoric Acid → Ancitabine

HRID 976092Notes

Reaction equation

[CH:1]1[C:7]([NH2:8])=[N:6][C:4](=O)[N:3]([C@@H:9]2[O:13][C@H:12]([CH2:14][OH:15])[C@@H:11]([OH:16])[C@@H:10]2[OH:17])[CH:2]=1.[C@@H]1(N2C=CC(N)=NC2=O)O[C@H](CO)[C@@H](O)[C@H]1O.P(=O)(O)(O)O>>[CH:1]1[C:7](=[NH:8])[N:6]=[C:4]2[N:3]([C@@H:9]3[O:13][C@H:12]([CH2:14][OH:15])[C@@H:11]([OH:16])[C@@H:10]3[O:17]2)[CH:2]=1

Participants

Reactant 3

HCID 1004Phosphoric Acid

HCID 6175Cytidine2×

HCID 6253Cytarabine

Product 1

HCID 25051Ancitabine

Procedure

Roberts et al (J. Org. Chem. 32, 816 (1967)) teach the production of cytarabine from cytidine (or from 2'(3')-cytidylic acid). Specifically, cytidine is reacted with phosphoric acid at 80° C. for a period of 30 hours to produce a 2,2'-O-cyclocytidine analogue intermediate. This intermediate is then hydrolyzed at a pH of 9 utilizing lithium hydroxide to produce the 3',5'-diphosphate of cytarabine. The diphosphate is then treated with magnesium chloride, ammonium chloride and concentrated ammonium hydroxide, and thereafter purified by column chromatography to yield pure cytarabine. The overall yield of pure cytarabine is limited to 53% based on the unrecovered portion of the starting cytidine.

Sources & evidence

ORD record: ord-da08f33e11294c5da4490e097905fba1
Source dataset: uspto-grants-1997_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05610292

Reaction notes

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