Cytarabine → Z-Val-Pro-Val-Pro Ara-C

HRID 882691Notes

Reaction equation

HRID 882691 reaction equation
[NH:1]([C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31])[C@H:2]([C:6]([N:8]1[CH2:29][CH2:28][CH2:27][C@H:9]1[C:10]([NH:12][C@H:13]([C:17]([N:19]1[CH2:26][CH2:25][CH2:24][C@H:20]1[C:21]([OH:23])=[O:22])=[O:18])[CH:14]([CH3:16])[CH3:15])=[O:11])=[O:7])[CH:3]([CH3:5])[CH3:4].ON1C2C=CC=CC=2N=N1.C(N=C=NC(C)C)(C)C.[CH:59]1[C:65]([NH2:66])=[N:64][C:62](=[O:63])[N:61]([C@@H:67]2[O:71][C@H:70]([CH2:72][OH:73])[C@@H:69]([OH:74])[C@@H:68]2[OH:75])[CH:60]=1>CN(C)C=O>[NH:1]([C:30]([O:32][CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)=[O:31])[C@H:2]([C:6]([N:8]1[CH2:29][CH2:28][CH2:27][C@H:9]1[C:10]([NH:12][C@H:13]([C:17]([N:19]1[CH2:26][CH2:25][CH2:24][C@H:20]1[C:21]([OH:23])=[O:22])=[O:18])[CH:14]([CH3:16])[CH3:15])=[O:11])=[O:7])[CH:3]([CH3:4])[CH3:5].[CH:59]1[C:65]([NH2:66])=[N:64][C:62](=[O:63])[N:61]([C@@H:67]2[O:71][C@H:70]([CH2:72][OH:73])[C@@H:69]([OH:74])[C@@H:68]2[OH:75])[CH:60]=1

Participants

6

Reactant 4

HCID 6253CytarabineHCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 131727672Z-Val-Pro-Val-Pro-OH

Product 1

HCID 131729867Z-Val-Pro-Val-Pro Ara-CYield 22%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of Z-Val-Pro-Val-Pro-OH [SEQ ID NO:9] (134.4 mg, 0.24 mmol) in dimethylformamide (1.5 mL), was successively treated at room temperature with 1-hydroxibenzotriazol (33.3 mg, 0.24 mmol), N,N′-diisopropylcarbodiimide (38.4 μL, 0.24 mmol) and Ara-C (50 mg, 0.20 mmol). The stirring was continued until complete disappearance of the starting material (overnight). Then, the solvent was evaporated, and 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 dryness leaving a residue that was purified by CCTLC on the chromatotron with dichloromethane:methanol (20:1) to give D (22% yield)

Workup

  1. customwas continued until complete disappearance of the starting material (overnight)
  2. customThen, the solvent was evaporated
  3. dissolutionthe residue was dissolved in ethyl acetate
  4. washwashed with citric acid (10%), NaHCO3 (10%) and brine
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. customevaporated to dryness
  7. customleaving a residue that
  8. customwas purified by CCTLC on the chromatotron with dichloromethane:methanol (20:1)
  9. customto give D (22% yield)

Sources & evidence

ORD record
ord-930f01ec93fd4852807e3b86c1423a95
Source dataset
uspto-grants-2012_08
Patent number
US08236756B2

Reaction notes

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