Hydrogen Bromide → HCID 178419602, compound

HRID 1076419Notes

Reaction equation

HRID 1076419 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:10]([OH:12])=O)[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:9])[NH2:8].[BrH:23].CO.[NH2:26][C@H:27]([C:35]([NH:37][C@H:38]([C:45]([NH:47][CH2:48][C:49]([O:51][CH3:52])=[O:50])=[O:46])[CH2:39][O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:36])[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O.C(Cl)Cl>[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:10]([NH:26][C@H:27]([C:35]([NH:37][C@H:38]([C:45]([NH:47][CH2:48][C:49]([O:51][CH3:52])=[O:50])=[O:46])[CH2:39][O:40][C:41]([CH3:43])([CH3:44])[CH3:42])=[O:36])[CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)=[O:12])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:9])[NH2:8].[BrH:23]

Participants

8

Reactant 5

HCID 260Hydrogen BromideHCID 887MethanolHCID 10868DicyclohexylcarbodiimideHCID 131710212HCID 131710212, compoundHCID 178512917HCID 178512917, compound

Product 1

HCID 178419602HCID 178419602, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

5.3 g of Z-Arg-OH (17.3 mmols) are suspended in 15 ml of dimethylformamide and after cooling with an ice-sodium chloride mixture, 5.9 ml of hydrobromic acid in methanol (3.06 N, 18 mmols) are added. After brief stirring a clear colourless solution is produced. A solution of 5.6 g of H-Phe-Ser(tBu)-Gly-OCH3 (14.4 mmols) in 15 ml of dimethylformamide is added dropwise thereto at -18°C and a further 7 ml of dimethylformamide are added. A solution of 3.85 g of dicyclohexylcarbodiimide in 5 ml of methylene chloride is then added, the cooling mixture is replaced by ice water after 1 hour, and after a further 3 hours the reaction mixture is stirred overnight at room temperature. The precipitate of dicyclohexylurea which has separated out is then filtered off and the filtrate is concentrated in vacuo to half its volume, cooled to 0°C and stirred into 600 ml of ether. The solution is decanted from the resulting precipitate, and the precipitate is washed with ether, dissolved in about 50 ml of methanol and again precipitated with 600 ml of ether. After again dissolving in methanol, the material is evaporated and dried in a high vacuum. In a thin layer chromatogram on silica gel layers the product shows: Rf52 = 0.48; Rf100 = 0.54; on Selekta cellulose Rf45 = 0.81.

Workup

  1. additionare added
  2. customis produced
  3. stirringafter a further 3 hours the reaction mixture is stirred overnight at room temperature
  4. customThe precipitate of dicyclohexylurea which has separated out
  5. filtrationis then filtered off
  6. concentrationthe filtrate is concentrated in vacuo to half its volume
  7. stirringstirred into 600 ml of ether
  8. customThe solution is decanted from the resulting precipitate
  9. washthe precipitate is washed with ether
  10. dissolutiondissolved in about 50 ml of methanol
  11. customagain precipitated with 600 ml of ether
  12. dissolutionAfter again dissolving in methanol
  13. customthe material is evaporated
  14. customdried in a high vacuum

Sources & evidence

ORD record
ord-d81b13bd912744e38a0bff7594c3f99e
Source dataset
uspto-grants-1976_05
Patent number
US03956260

Reaction notes

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