Hydrochloric Acid → HCID 178427547, compound

HRID 723013Notes

Reaction equation

HRID 723013 reaction equation
Cl.[NH2:2][C@H:3]([C:21]([N:23]1[CH2:42][CH2:41][CH2:40][C@H:24]1[C:25]([NH:27][C@H:28]([C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31])[CH3:29])=[O:26])=[O:22])[CH2:4][CH2:5][CH2:6][NH:7][C:8](=[NH:20])[NH:9][S:10]([C:13]1[CH:19]=[CH:18][C:16]([CH3:17])=[CH:15][CH:14]=1)(=[O:12])=[O:11].[NH:43]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[C@H:44]([C:46](O)=[O:47])[CH3:45].ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1.C(Cl)(Cl)Cl.CO>[NH:43]([C:49]([O:51][C:52]([CH3:53])([CH3:55])[CH3:54])=[O:50])[C@H:44]([C:46]([NH:2][C@H:3]([C:21]([N:23]1[CH2:42][CH2:41][CH2:40][C@H:24]1[C:25]([NH:27][C@H:28]([C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31])[CH3:29])=[O:26])=[O:22])[CH2:4][CH2:5][CH2:6][NH:7][C:8](=[NH:20])[NH:9][S:10]([C:13]1[CH:14]=[CH:15][C:16]([CH3:17])=[CH:18][CH:19]=1)(=[O:11])=[O:12])=[O:47])[CH3:45]

Participants

8

Reactant 5

HCID 313Hydrochloric Acid2×HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 85082Tert-butoxycarbonylalanineHCID 178427561HCID 178427561, compound2×

Product 1

HCID 178427547HCID 178427547, compoundYield 54%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21584188Chloroform methanolSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C. the solution of 45 mg (0.072 mmol) of HCl.Arg(Tos)-Pro-Ala-OBzl in 15 ml of anhydrous tetrahydrofuran was adjusted to pH 9, to which the pre-cold solution of 15 mg (0.079 mmol) Boc-Ala-OH, 10 mg (0.074 mmol) of 1-hydroxybenzotriazole and 16 mg (0.077 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.Arg(Tos)-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 30 mg (54%) of the title compound as a colorless powder. Mp 80–82° C., FAB-MS (m/e) 758[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-55fbe66b0abb48f9905135f48eb04836
Source dataset
uspto-grants-2006_11
Patent number
US07138491B2

Reaction notes

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