Dicyclohexylcarbodiimide → HCID 178481530, compound

HRID 2413703Notes

Reaction equation

HRID 2413703 reaction equation
Br.Br.[NH2:3][C@H:4]([C:11]([N:13]1[CH2:20][CH2:19][CH2:18][C@H:14]1[C:15]([NH2:17])=[O:16])=[O:12])[CH2:5][C:6]1[N:10]=[CH:9][NH:8][CH:7]=1.[CH3:21][N:22]1[C:25](=[O:26])[CH2:24][C@H:23]1[C:27](O)=[O:28].C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C.C(N(CC)CC)C>[OH2:12].[NH3:3].[CH3:21][N:22]1[C:25](=[O:26])[CH2:24][C@H:23]1[C:27]([NH:3][C@H:4]([C:11]([N:13]1[CH2:20][CH2:19][CH2:18][C@H:14]1[C:15]([NH2:17])=[O:16])=[O:12])[CH2:5][C:6]1[N:10]=[CH:9][NH:8][CH:7]=1)=[O:28]

Participants

8

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 54390892HCID 54390892, compoundHCID 178419276HCID 178419276, compound

Product 2

HCID 12896473Azane;hydrateHCID 178481530HCID 178481530, compoundYield 97.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

In 25 ml of dry DMF was suspended 826 mg of L-histidyl-L-prolinamide dihydrobromide (4) and 0.557 ml of triethylamine was dropwise added slowly to the suspension at -15° to -10° C. After stirring the mixture at the same temperature for 30 minutes, insoluble materials were filtered off under cooling to obtain a clear filtrate. To the filtrate were added 258 mg of compound (12), 351 mg of HOBT and 453 mg of DCC at -10° C. After stirring the mixture at -10° to 0° C. for 2 hours, the mixture was allowed to stand in a refrigerator for 2 days. After the precipitated insoluble matters were filtered off, the solvent was removed by distillation under reduced pressure. The resulting residue was subjected to column chromatography using 150 ml of silica gel (Wakogel C-200). By eluting with chloroform-methanol-conc. ammonia water (40:10:1), 352.6 mg of Nα -[(S)-1 -methyl-4-oxo-2-azetidinylcarbonyl]-L-histidyl-L-prolinamide (13) was obtained.

Workup

  1. additionwas dropwise added slowly to the suspension at -15° to -10° C
  2. filtrationinsoluble materials were filtered off
  3. temperatureunder cooling
  4. customto obtain a clear filtrate
  5. stirringAfter stirring the mixture at -10° to 0° C. for 2 hours
  6. waitto stand in a refrigerator for 2 days
  7. filtrationAfter the precipitated insoluble matters were filtered off
  8. customthe solvent was removed by distillation under reduced pressure
  9. washBy eluting with chloroform-methanol-conc

Sources & evidence

ORD record
ord-6782fafa00b54cf0a4462c4fce834a45
Source dataset
uspto-grants-1988_01
Patent number
US04719207

Reaction notes

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