Dicyclohexylcarbodiimide → HCID 178465169, compound

HRID 845378Notes

Reaction equation

HRID 845378 reaction equation
[NH:1]([C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])[C@H:2]([C:13]([OH:15])=O)[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:12])[NH:8][N+:9]([O-:11])=[O:10].ON1C2C=CC=CC=2N=N1.[CH2:36]([NH:38][C:39](=[O:45])[C@@H:40]1[CH2:44][CH2:43][CH2:42][NH:41]1)[CH3:37].C1CCC(N=C=NC2CCCCC2)CC1>C1COCC1>[NH:1]([C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])[C@H:2]([C:13]([N:41]1[CH2:42][CH2:43][CH2:44][C@H:40]1[C:39]([NH:38][CH2:36][CH3:37])=[O:45])=[O:15])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:12])[NH:8][N+:9]([O-:11])=[O:10]

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 74086092-Pyrrolidinecarboxamide,N-ethyl-,(2S)-(9CI)HCID 178512185HCID 178512185, compound

Product 1

HCID 178465169HCID 178465169, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

7.33 g (29.7 mmoles) of Z-Arg(NO2)-OH and 1.034 g of N-hydroxy-benzotriazole are added to a solution containing 3.24 g (22.8 mmoles) of proline ethylamide in 70 ml of THF. The reaction mixture is cooled in an iced water bath and 5.34 g (25.8 mmoles) of DCC dissolved in 50 ml of THF are portionwise added under stirring. The mixture is stirred under cooling with ice for 5 hours, at room temperature for additional 20 hours, then filtered and washed with THF. The filtrate is evaporated under reduced pressure, the residue is dissolved in chloroform and successively washed 3 times with 35 ml of an 1:5 mixture of ammonium hydroxide with water each, twice with 20 ml of water each, 3 times with 35 ml of 1N hydrochloric acid each and finally twice with 20 ml of water each. The chloroformic solution is dried over anhydrous sodium sulfate, filtered, washed with chloroform, then the filtrate is evaporated. The residue is dissolved in a mixture of 35 ml of THF and 50 ml of ethyl acetate, filtered and washed with 30 ml of an 1:2 mixture of THF with ethyl acetate. After evaporating the solution, 100 ml of ethyl ether are added to the solid foamy residue. The thus-obtained product is filtered, washed with ether and dried under reduced pressure to afford 9.69 g (98% yield) of the aimed compound, m.p.: 125° C.

Workup

  1. temperatureThe reaction mixture is cooled in an iced water bath
  2. additionare portionwise added
  3. stirringThe mixture is stirred
  4. filtrationfiltered
  5. washwashed with THF
  6. customThe filtrate is evaporated under reduced pressure
  7. dissolutionthe residue is dissolved in chloroform
  8. washsuccessively washed 3 times
  9. additionwith 35 ml of an 1:5 mixture of ammonium hydroxide with water each, twice with 20 ml of water each, 3 times with 35 ml of 1N hydrochloric acid each and finally twice with 20 ml of water each
  10. dry with materialThe chloroformic solution is dried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. washwashed with chloroform
  13. customthe filtrate is evaporated
  14. dissolutionThe residue is dissolved in a mixture of 35 ml of THF and 50 ml of ethyl acetate
  15. filtrationfiltered
  16. washwashed with 30 ml of an 1:2 mixture of THF with ethyl acetate
  17. customAfter evaporating the solution, 100 ml of ethyl ether
  18. additionare added to the solid foamy residue
  19. filtrationThe thus-obtained product is filtered
  20. washwashed with ether
  21. customdried under reduced pressure

Sources & evidence

ORD record
ord-93bb9a765b3b497fbfc31d2586b4275c
Source dataset
uspto-grants-1988_07
Patent number
US04758552

Reaction notes

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