Hydrochloric Acid → HCID 178427589, compound

HRID 723012Notes

Reaction equation

HRID 723012 reaction equation
Cl.[NH:2]1[CH2:21][CH2:20][CH2:19][C@H:3]1[C:4]([NH:6][C@H:7]([C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])[CH3:8])=[O:5].[NH:22]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C@H:23]([C:41](O)=[O:42])[CH2:24][CH2:25][CH2:26][NH:27][C:28](=[NH:40])[NH:29][S:30]([C:33]1[CH:39]=[CH:38][C:36]([CH3:37])=[CH:35][CH:34]=1)(=[O:32])=[O:31].ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1.C(Cl)(Cl)Cl.CO>[NH:22]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C@H:23]([C:41]([N:2]1[CH2:21][CH2:20][CH2:19][C@H:3]1[C:4]([NH:6][C@H:7]([C:9]([O:11][CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)=[O:10])[CH3:8])=[O:5])=[O:42])[CH2:24][CH2:25][CH2:26][NH:27][C:28](=[NH:40])[NH:29][S:30]([C:33]1[CH:39]=[CH:38][C:36]([CH3:37])=[CH:35][CH:34]=1)(=[O:32])=[O:31]

Participants

8

Reactant 5

HCID 313Hydrochloric Acid2×HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 83767L-Ornithine, N2-[(1,1-dimethylethoxy)carbonyl]-N5-[imino[[(4-methylphenyl)sulfonyl]amino]methyl]-HCID 53994593HCID 53994593, compound2×

Product 1

HCID 178427589HCID 178427589, compoundYield 75.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21584188Chloroform methanolSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C. the solution of 72 mg (0.231 mmol) of HCl.Pro-Ala-OBzl in 15 ml of anhydrous tetrahydrofuran was adjusted to pH 9, to which the pre-cold solution of 100 mg (0.234 mmol) of Boc-Arg(Tos)-OH, 31 mg (0.230 mmol) of 1-hydroxybenzotriazole and 48 mg (0.233 mmol) of dicyclohexylcarbodiimide in 20 ml of anhydrous tetrahydrofuran was added. The reaction mixture was stirred at 0° C. for 2 h and at room temperature for 6 h and TLC (chloroform/methanol, 30:1) indicated complete disappearance of HCl.Pro-Ala-OBzl. The resulted precipitates of N,N-dicyclohexylurea were filtrated and the filtrate was diluted with 80 ml of ethyl acetate. The solution obtained was washed successively with saturated NaCO3 in water (50 ml×3), saturated NaCl in water (50 ml×3) and KHSO4 in water (5%, 30 ml×3). The separated ethyl acetate layer was dried with anhydrous MgSO4, and then evaporated to provide 120 mg (75.6%) of the title compound as a colorless powder. Mp70–71.5° C., FAB-MS (m/e) 688[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 80 ml of ethyl acetate
  6. customThe solution obtained
  7. washwas washed successively with saturated NaCO3 in water (50 ml×3), saturated NaCl in water (50 ml×3)
  8. dry with materialThe separated ethyl acetate layer was dried with anhydrous MgSO4
  9. customevaporated

Sources & evidence

ORD record
ord-a05277d5434e4496b7057158c7a48ef0
Source dataset
uspto-grants-2006_11
Patent number
US07138491B2

Reaction notes

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