Hydrochloric Acid → HCID 131726071, compound

HRID 722985Notes

Reaction equation

HRID 722985 reaction equation
Cl.[NH2:2][C@H:3]([C:5]([NH:7][C@H:8]([C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])[CH2:9][CH2:10][CH2:11][CH2:12][NH:13][C:14]([O:16][CH2:17][C:18]1[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=1[Cl:20])=[O:15])=[O:6])[CH3:4].[N:35]1([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:42][CH2:41][CH2:40][C@H:36]1[C:37](O)=[O:38].ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1.C(Cl)(Cl)Cl.CO>[N:35]1([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:42][CH2:41][CH2:40][C@H:36]1[C:37]([NH:2][C@H:3]([C:5]([NH:7][C@H:8]([C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])[CH2:9][CH2:10][CH2:11][CH2:12][NH:13][C:14]([O:16][CH2:17][C:18]1[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=1[Cl:20])=[O:15])=[O:6])[CH3:4])=[O:38]

Participants

8

Reactant 5

HCID 313Hydrochloric Acid2×HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 131726072HCID 131726072, compound2×

Product 1

HCID 131726071HCID 131726071, compoundYield 98%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21584188Chloroform methanolSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C. the solution of 657 mg (1.28 mmol) of HCl.Ala-Lys(ClZ)-OBzl in 5 ml of anhydrous tetrahydrofuran was adjusted to pH 9, to which the pre-cold solution of 280 mg (1.3 mmol) of Boc-Pro-OH, 170 mg (1.26 mmol) of 1-hydroxybenzotriazole and 270 mg (1.31 mmol) of dicyclohexylcarbodiimide in 30 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, 20:1) indicated complete disappearance of HCl.Ala-Lys(ClZ)-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 134 mg (98%) of the title compound as a colorless powder. Mp86–88° C., FAB-MS (m/e) 674[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-2421226033764d76b6c7837cbee02081
Source dataset
uspto-grants-2006_11
Patent number
US07138491B2

Reaction notes

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