Hydrochloric Acid → HCID 178427590, compound

HRID 723008Notes

Reaction equation

HRID 723008 reaction equation
[NH:1]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C@H:2]([C:20](O)=[O:21])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:19])[NH:8][S:9]([C:12]1[CH:18]=[CH:17][C:15]([CH3:16])=[CH:14][CH:13]=1)(=[O:11])=[O:10].ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1.Cl.N[C@H](C(N1CCC[C@H]1C(N[C@H](C([NH:86][C@H:87]([C:104]([O:106][CH2:107][C:108]1[CH:113]=[CH:112][CH:111]=[CH:110][CH:109]=1)=[O:105])[CH2:88][CH2:89][CH2:90]CNC(OCC1C=CC=CC=1Cl)=O)=O)C)=O)=O)CCCNC(=N)NS(C1C=CC(C)=CC=1)(=O)=O>O1CCCC1.C(Cl)(Cl)Cl.CO>[NH:1]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C@H:2]([C:20]([N:86]1[CH2:90][CH2:89][CH2:88][C@H:87]1[C:104]([O:106][CH2:107][C:108]1[CH:113]=[CH:112][CH:111]=[CH:110][CH:109]=1)=[O:105])=[O:21])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:19])[NH:8][S:9]([C:12]1[CH:13]=[CH:14][C:15]([CH3:16])=[CH:17][CH:18]=1)(=[O:10])=[O:11]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 83767L-Ornithine, N2-[(1,1-dimethylethoxy)carbonyl]-N5-[imino[[(4-methylphenyl)sulfonyl]amino]methyl]-HCID 178427560Arg(Tos)-Pro-Ala-Lys(ClZ)-OBzl

Product 1

HCID 178427590HCID 178427590, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21584188Chloroform methanolSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C. the solution of 18 mg (0.075 mmol) of HCl Pro-OBzl in 5 ml of anhydrous tetrahydrofuran was adjusted to pH 9, to which the pre-cold solution of 33 mg (0.077 mmol) Boc-Arg(Tos)-OH, 10 mg (0.074 mmol) of 1-hydroxybenzotriazole and 16 mg (0.077 mmol) of dicyclohexylcarbodiimide in 10 ml of anhydrous tetrahydrofuran was added. The reaction mixture was stirred at 0° C. for 2 h and at room temperature for 5 h and TLC (chloroform/methanol, 30:1) indicated complete disappearance of HCl.Arg(Tos)-Pro-Ala-Lys(ClZ)-OBzl (SEQ ID NO: 12). The resulted precipitates of N,N-dicyclohexylurea were filtrated and the filtrate was diluted with 30 ml of ethyl acetate. The solution obtained was washed successively with saturated NaCO3 in water (10 ml×3), saturated NaCl in water (10 ml×3) and KHSO4 in water (5%, 10 ml×3). The separated ethyl acetate layer was dried with anhydrous MgSO4, filtered. The filtrate was evaporated to provide 37 mg (80%) of the title compound as a colorless powder. Mp 60–62° C., FAB-MS (m/e) 617[M+H]+.

Workup

  1. customAt 0° C.
  2. additionwas added
  3. customThe resulted precipitates of N,N-dicyclohexylurea
  4. filtrationwere filtrated
  5. additionthe filtrate was diluted with 30 ml of ethyl acetate
  6. customThe solution obtained
  7. washwas washed successively with saturated NaCO3 in water (10 ml×3), saturated NaCl in water (10 ml×3)
  8. dry with materialThe separated ethyl acetate layer was dried with anhydrous MgSO4
  9. filtrationfiltered
  10. customThe filtrate was evaporated

Sources & evidence

ORD record
ord-28c189e0bfbc43c988bbe1edd5b5c7c5
Source dataset
uspto-grants-2006_11
Patent number
US07138491B2

Reaction notes

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