Dicyclohexylcarbodiimide → N,N'-Dicyclohexylurea

HRID 1976540Notes

Reaction equation

HRID 1976540 reaction equation
CC[C@@]1(O)C(=O)[O:7]CC2C(N3C(=CC1=2)C1N=C2C(C=CC=C2)=CC=1C3)=O.[CH2:27]1[CH2:32][CH2:31][CH:30]([N:33]=[C:34]=[N:35][CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)[CH2:29][CH2:28]1>CN(C1C=CN=CC=1)C.CN(C=O)C>[CH:36]1([NH:35][C:34](=[O:7])[NH:33][CH:30]2[CH2:29][CH2:28][CH2:27][CH2:32][CH2:31]2)[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1

Participants

5

Reactant 2

HCID 10868DicyclohexylcarbodiimideHCID 24360Camptothecin

Product 1

HCID 4277N,N'-Dicyclohexylurea

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

The preparation is preferably carried out in the following way: The starting camptothecin compound, preferably 2 to 10 molar equivalent of the reacting aromatic acid of the general formula C6R2-6COOH, preferably 2 to 8 molar equivalent of DCC, and a catalytic amount of DMAP are added to about 60-100 ml DMF in a 250 ml round-bottomed flask equipped with a mechanical stirrer. The mixture is stirred at room temperature under nitrogen gas for 72-96 hr. Dicyclohexyl urea formed is removed by filtration. The filtrate is poured onto 500-800 ml ice water while stirring. The crude product is collected by filtration, air-dried at room temperature, then separated by column chromatography with THF-C2H2 (from 1:7 to 1:15) as eluent. The pure ester prodrug is obtained as white or yellow powders after precipitation from petroleum ether. Reaction yields can range from 5 to 98%.

Workup

  1. customequipped with a mechanical stirrer

Sources & evidence

ORD record
ord-55c7ce9262f54d67abe9c1f8d58ec13f
Source dataset
uspto-grants-2001_05
Patent number
US06228855B1

Reaction notes

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