Cytarabine → urea Ara-C

HRID 842586Notes

Reaction equation

HRID 842586 reaction equation
NN.Cl.Cl.ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.CCN(C(C)C)C(C)C.[CH:26]1[C:32]([NH2:33])=[N:31][C:29](=[O:30])[N:28]([C@@H:34]2[O:38][C@H:37]([CH2:39][OH:40])[C@@H:36]([OH:41])[C@@H:35]2[OH:42])[CH:27]=1>C1(C)C=CC=CC=1.CN(C1C=CN=CC=1)C.N1C=CC=CC=1.C(OCC)C>[NH2:28][C:29]([NH2:31])=[O:30].[CH:26]1[C:32]([NH2:33])=[N:31][C:29](=[O:30])[N:28]([C@@H:34]2[O:38][C@H:37]([CH2:39][OH:40])[C@@H:36]([OH:41])[C@@H:35]2[OH:42])[CH:27]=1

Participants

9

Reactant 4

HCID 6253CytarabineHCID 17548Hydrazine, dihydrochlorideHCID 81531DiisopropylethylamineHCID 94429Triphosgene

Product 1

HCID 131723191urea Ara-C

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolventHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
30 °C

Procedure

A solution of PEG-diamine dihydrochloride (6), (3.0 g, 0.08 mmol) in 80 mL of toluene is azeotroped for 2 hours. The solution is cooled to 30° C. followed by the addition of triphosgene (0.02 g, 0.06 mmol) and DIEA (0.07 g, 0.5 mmol). This mixture is stirred for 3 hours at 70-80° C. followed by cooling to room temperature and addition of 60 mL of ethyl ether. PEG-isocyanate (7) is collected by filtration under nitrogen, and immediately added to a solution of 1 (0.27 g, 1.1 mmol) and DMAP (0.14 g, 1.1 mmol) in anhydrous pyridine (30 mL) and the reaction is stirred at 45° C. overnight. The solvent is removed in vacuo, and the residue is crystallized from IPA to yield PEG-urea-Ara-C (8).

Workup

  1. temperatureby cooling to room temperature
  2. filtrationPEG-isocyanate (7) is collected by filtration under nitrogen
  3. stirringthe reaction is stirred at 45° C. overnight
  4. customThe solvent is removed in vacuo
  5. customthe residue is crystallized from IPA

Sources & evidence

ORD record
ord-1c22f2ab4521475e878d44b933e7befc
Source dataset
uspto-grants-2002_04
Patent number
US06376470B1

Reaction notes

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