Dicyclohexylcarbodiimide → HCID 178446040, compound

HRID 1982339Notes

Reaction equation

HRID 1982339 reaction equation
[NH:1]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C@H:2]([C@H:7]([CH2:9][C:10]([OH:12])=O)[OH:8])[CH2:3][CH:4]([CH3:6])[CH3:5].[NH2:23][CH2:24][CH2:25][C:26]([NH:28][C@H:29]([C:36](N)=[O:37])[CH2:30][C:31]1[N:35]=[CH:34][NH:33][CH:32]=1)=[O:27].C1C=CC2N([OH:48])N=[N:45]C=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C.O>[NH:1]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C@H:2]([C@H:7]([CH2:9][C:10]([NH:23][CH2:24][CH2:25][C:26]([NH:28][C@H:29]([C:36]([OH:37])=[O:48])[CH2:30][C:31]1[N:35]=[CH:34][NH:33][CH:32]=1)=[O:27])=[O:12])[OH:8])[CH2:3][CH:4]([CH3:5])[CH3:6].[NH3:45]

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 14560231Z-Sta-OHHCID 178511197HCID 178511197, compound

Product 1

HCID 178446040HCID 178446040, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

370 mg of Z-Sta-OH, 225 mg of H-β-Ala-His-NH2, 153 mg of HOBt×H2O and 247 mg of DCCI are suspended in 4.5 ml of DMF and stirred at room temperature. After approximately 10 minutes a clear solution has formed and afrer approximately 20 minutes DCH begins to crystallize out. The mixture is left to stand overnight, then stirred for 30 minutes at 0°, DCH is filtered off und the filtrate is concentrated to an oil. This is heated for 1 hour at 60° in 14 ml of methanol/glacial acetic acid/H2O (94:3:3), the solution is concentrated to 3 ml and the crude product is precipitated by 30 ml of diisopropyl ether and dried. To remove the acetic acid, the residue is dissolved in n-butanol, washed in succession with 5% strength NaHCO3 solution and with water, and the butanol phase is again concentrated to dryness. After purification by chromatography over 30 g of silica gel (Merck No. 60, 230-400 mesh) using as eluant chloroform/methanol (75:25), Z-Sta-β-Ala-His-NH3 is obtained; Rf (G)=0.28.

Workup

  1. customAfter approximately 10 minutes a clear solution has formed and afrer approximately 20 minutes DCH
  2. customto crystallize out
  3. waitThe mixture is left
  4. stirringstirred for 30 minutes at 0°
  5. filtrationDCH is filtered off und the filtrate
  6. concentrationis concentrated to an oil
  7. temperatureThis is heated for 1 hour at 60° in 14 ml of methanol/glacial acetic acid/H2O (94:3:3)
  8. concentrationthe solution is concentrated to 3 ml
  9. customthe crude product is precipitated by 30 ml of diisopropyl ether
  10. customdried
  11. customTo remove the acetic acid
  12. dissolutionthe residue is dissolved in n-butanol
  13. washwashed in succession with 5% strength NaHCO3 solution and with water
  14. concentrationthe butanol phase is again concentrated to dryness
  15. customAfter purification by chromatography over 30 g of silica gel (Merck No. 60, 230-400 mesh)

Sources & evidence

ORD record
ord-20240a15e979448e823e073bc5cae017
Source dataset
uspto-grants-1986_06
Patent number
US04595677

Reaction notes

Loading…