Cytarabine → Boc-Val-Pro Ara-C

HRID 882690Notes

Reaction equation

HRID 882690 reaction equation
[NH:1]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C@H:2]([C:6]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10]([OH:12])=[O:11])=[O:7])[CH:3]([CH3:5])[CH3:4].ON1C2C=CC=CC=2N=N1.CC(N=C=NC(C)C)C.[CH:42]1[C:48]([NH2:49])=[N:47][C:45](=[O:46])[N:44]([C@@H:50]2[O:54][C@H:53]([CH2:55][OH:56])[C@@H:52]([OH:57])[C@@H:51]2[OH:58])[CH:43]=1>CN(C)C=O>[NH:1]([C:16]([O:18][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:17])[C@H:2]([C:6]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10]([OH:12])=[O:11])=[O:7])[CH:3]([CH3:5])[CH3:4].[CH:42]1[C:48]([NH2:49])=[N:47][C:45](=[O:46])[N:44]([C@@H:50]2[O:54][C@H:53]([CH2:55][OH:56])[C@@H:52]([OH:57])[C@@H:51]2[OH:58])[CH:43]=1

Participants

6

Reactant 4

HCID 6253CytarabineHCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 11045256Boc-Val-Pro-OH

Product 1

HCID 131729866Boc-Val-Pro Ara-CYield 21%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of Boc-Val-Pro-OH (94.5 mg, 0.30 mmol) in dimethylformamide (1.5 mL), was successively treated, at room temperature, with 1-hydroxibenzotriazol (40.5 mg, 0.30 mmol), N,N-diisopropylcarbodiimide (46.7 μL, 0.30 mmol) and Ara-C (60.9 mg, 0.25 mmol). The stirring was continued until complete disappearance of the starting material (overnight stirring). Then, the solvent was evaporated, the residue was dissolved in ethyl acetate and washed with citric acid (10%), NaHCO3 (10%) and brine. The organic layer was dried (Na2SO4) and evaporated to give a residue that was purified by CCTLC on the chromatotron with dichloromethane:methanol (20:1) to yield Ara-C-dipeptide (A) (21% yield)

Workup

  1. customThen, the solvent was evaporated
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. washwashed with citric acid (10%), NaHCO3 (10%) and brine
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. customevaporated
  6. customto give a residue that
  7. customwas purified by CCTLC on the chromatotron with dichloromethane:methanol (20:1)

Sources & evidence

ORD record
ord-19aa42d2510541c3b7f6244579222e7a
Source dataset
uspto-grants-2012_08
Patent number
US08236756B2

Reaction notes

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