Uridine → Nelarabine

HRID 1736055

Reaction equation

HRID 1736055 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([O:11][CH3:12])[N:3]=1.[H-].[Na+].C1C(=O)NC(=O)N([C@@H:23]2[O:27][C@H:26]([CH2:28][OH:29])[C@@H:25]([OH:30])[C@@H:24]2[OH:31])C=1.[C@@H]1(N2C=CC(=O)NC2=O)O[C@H](CO)[C@@H](O)[C@H]1O>O1CCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(O)CC.CO>[C@@H:23]1([N:8]2[CH:7]=[N:6][C:5]3[C:9]2=[N:10][C:2]([NH2:1])=[N:3][C:4]=3[O:11][CH3:12])[O:27][C@H:26]([CH2:28][OH:29])[C@@H:25]([OH:30])[C@@H:24]1[OH:31]

Participants

9

Reactant 4

HCID 6029UridineHCID 18323Uracil ArabinosideHCID 24758Sodium hydrideHCID 65275O-(6)-Methylguanine

Product 1

HCID 3011155Nelarabine

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 10311-PropanolSolventHCID 8028TetrahydrofuranSolventHCID 62657Potassium Phosphate, TribasicSolvent

Procedure

2-Amino-6-methoxypurine (prepared by nucleophilic displacement of the chlorine group on 2-amino-6-chloropurine(Sigma Chemicals, St. Louis, Mo.) by methanol with sodium hydride in tetrahydrofuran) (6.4 mmoles, 1.05 g) was combined with 35 ml of a uracil arabinoside solution (7.04 mmoles, 1.75 g) in 10 mM potassium phosphate and 7% n-propanol (v/v). The pH was adjusted to 6.75. Purified purine nucleoside phosphorylase (18000 units) and uridine phosphorylase (1020 units) were added and the solution incubated at 37° C. After 26 days the reaction was filtered and the filtrate chromatographed on a column of Dowex-1-formate resin (2×7 cm) after adjusting the pH to 10.5 with concentrated ammonium hydroxide. The column was eluted with 7% n-propanol/water (v/v) and fractions containing product were combined and solvent removed in vacuo. The residue was extracted with 25 ml of water and the filtrate separated from the solids by centrifugation. The supernatant upon standing at ambient temperature formed crystals of 9-β-D-arabinofuranosyl-2-amino-6-methoxy-9 H-purine which after drying in vacuo, yielded 0.327 g of product. NMR and mass spectrometry were consistent with the structure.

Workup

  1. customincubated at 37° C
  2. filtrationAfter 26 days the reaction was filtered
  3. customthe filtrate chromatographed on a column of Dowex-1-formate resin (2×7 cm)
  4. washThe column was eluted with 7% n-propanol/water (v/v) and fractions
  5. additioncontaining product
  6. customsolvent removed in vacuo
  7. extractionThe residue was extracted with 25 ml of water
  8. customthe filtrate separated from the solids by centrifugation
  9. customupon standing at ambient temperature

Sources & evidence

ORD record
ord-e7f318e60ba8487c893a62806623664d
Source dataset
uspto-grants-1996_07
Patent number
US05539098

Linked notes

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