HCID 178507914, compound → Cytarabine

HRID 548513Notes

Reaction equation

HRID 548513 reaction equation
O=[CH:2][C@H:3]([C@@H:5]([C@@H:7]([CH2:9][OH:10])[OH:8])[OH:6])[OH:4].[NH:11]1[CH:18]=[CH:17][C:15]([NH2:16])=[N:14][C:12]1=[O:13]>N1C=CC=CC=1>[CH:17]1[C:15]([NH2:16])=[N:14][C:12](=[O:13])[N:11]([C@@H:2]2[O:8][C@H:7]([CH2:9][OH:10])[C@@H:5]([OH:6])[C@@H:3]2[OH:4])[CH:18]=1

Participants

3

Reactant 1

HCID 178507914HCID 178507914, compound

Product 1

HCID 6253Cytarabine

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

M-PEOZ-O—CH2—CO2—NHS (M-PEOZ-SCM 5000) (180 mg, 0.034 mmol) was dissolved in 11 mL of pyridine and added to a solution of cytosine arabinose (Ara-C) (5.7 mg, 0.023 mmol), previously dissolved in 5 mL of anhydrous pyridine at 0° C. The resulting solution stirred for 72 hours at room temperature. Reverse phase HPLC (C-18 column) showed that reaction was complete. After evaporation of the solvent, the product was dissolved in methylene chloride (5 mL) and added drop by drop into 150 mL ether. The precipitate was collected by centrifugation at 4° C. and dried under vacuum. Yield 150 mg, 80%. NMR showed the usual peaks of the M-PEOZ backbone (above) plus the pyrimidine protons of Ara-C at 7.31, 7.67, 8.16, and 8.62 ppm. Exposure of the conjugate to pH 8 buffer showed that Ara-C is slowly released (15% after 24 hours), so the conjugate can be regarded as a prodrug.

Workup

  1. customReverse phase HPLC (C-18 column) showed that reaction
  2. customAfter evaporation of the solvent
  3. dissolutionthe product was dissolved in methylene chloride (5 mL)
  4. additionadded drop by drop into 150 mL ether
  5. customThe precipitate was collected by centrifugation at 4° C.
  6. customdried under vacuum
  7. custom(15% after 24 hours)

Sources & evidence

ORD record
ord-c876c0b736b44c6ea6df81daee5c4e02
Source dataset
uspto-grants-2011_05
Patent number
US07943141B2

Reaction notes

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