Penicillin V → N,N'-Dicyclohexylurea

HRID 1587641

Reaction equation

HRID 1587641 reaction equation
CC1(C)S[C@@H]2[C@H](NC(COC3C=CC=CC=3)=O)C(=[O:9])N2[C@H]1C(O)=O.CN(C1C=CC=CN=1)C.[CH2:34]1[CH2:39][CH2:38][CH:37]([N:40]=[C:41]=[N:42][CH:43]2[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]2)[CH2:36][CH2:35]1>C(Cl)Cl>[CH:43]1([NH:42][C:41](=[O:9])[NH:40][CH:37]2[CH2:36][CH2:35][CH2:34][CH2:39][CH2:38]2)[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]1

Participants

5

Reactant 3

HCID 6869Penicillin VHCID 10868DicyclohexylcarbodiimideHCID 218852-Dimethylaminopyridine

Product 1

HCID 4277N,N'-Dicyclohexylurea

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 10 mL round-bottomed flask, 0.400 g (0.178 mmol) of the poly(PEG-Lys) having ethanolamide pendant functional groups of Example 6 was dissolved in 4 mL of methylene chloride. To this solution was added 0.094 g (0.267 mmol) of Penicillin V (Sigma) and 0.008 g (0.065 mmol) of dimethylaminopyridine (Aldrich). The reaction mixture was cooled in an ice water bath and then 0.048 g (0.232 mmol) of DCC was added. After a few hours at 0° C., the reaction vessel was moved to a cold room maintained at 420 C. and allowed to stir for almost six days. A precipitate of dicyclohexyl urea formed and was removed by filtration. The drug conjugate was precipitated with cold ether. About 0.250 g of crude product was obtained which was purified by reprecipitation twice from isopropanol. TLC in methanol showed absence of free drug.

Workup

  1. temperatureThe reaction mixture was cooled in an ice water bath
  2. waitAfter a few hours at 0° C.
  3. temperaturemaintained at 420 C

Sources & evidence

ORD record
ord-cfe48a704ad8418e8623c1335992e307
Source dataset
uspto-grants-1993_06
Patent number
US05219564

Linked notes

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