Triethylamine → HCID 178449997, compound

HRID 2372639Notes

Reaction equation

HRID 2372639 reaction equation
CC(C)(OC(N[C@H](C(O)=O)CC1N(COCC2C=CC=CC=2)C=NC=1)=O)C.[ClH:28].NC(C(O)CC1CCCCC1)C(O)CS(NCCCC)(=O)=O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.[CH3:68][C:69]([CH3:115])([O:71][C:72]([NH:74][C@H:75]([C:91]([NH:93][CH:94]([CH2:108][CH:109]1[CH2:114][CH2:113][CH2:112][CH2:111][CH2:110]1)[CH:95]([OH:107])[CH:96]([OH:106])[CH2:97][S:98]([NH:101][CH2:102][CH2:103][CH2:104][CH3:105])(=[O:100])=[O:99])=[O:92])[CH2:76][C:77]1[N:81](COCC2C=CC=CC=2)[CH:80]=[N:79][CH:78]=1)=[O:73])[CH3:70]>CN(C)C=O.ClCCl.CO>[ClH:28].[CH3:115][C:69]([CH3:68])([O:71][C:72]([NH:74][C@H:75]([C:91]([NH:93][CH:94]([CH2:108][CH:109]1[CH2:114][CH2:113][CH2:112][CH2:111][CH2:110]1)[CH:95]([OH:107])[CH:96]([OH:106])[CH2:97][S:98]([NH:101][CH2:102][CH2:103][CH2:104][CH3:105])(=[O:99])=[O:100])=[O:92])[CH2:76][C:77]1[N:81]=[CH:80][NH:79][CH:78]=1)=[O:73])[CH3:70]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 7023105HCID 7023105, compoundHCID 86749728HCID 86749728, compoundHCID 131717212HCID 131717212, compound2×

Product 1

HCID 178449997HCID 178449997, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

N-[(1,1-Dimethylethoxy)carbonyl]-3-[(phenylmethoxy)methyl]-L-histidine (101 mg., 0.268 mmole, 1 eq.) and [βR-(βR*,δR*,γS*)-γ-amino-N-butyl-β,δ-dihydroxycyclohexanepentanesulfonamide, monohydrochloride (100 mg., 0.268 mmole, 1 eq., product of Example 1) were dissolved in dimethylformamide under an argon atmosphere. The solution was cooled to 0° and treated with 1-hydroxybenzotriazole (36 mg., 0.268 mmole, 1 eq.), triethylamine (56 μl, 0.402 mmole, 1.5 eq.) and ethyl-3-(3-dimethylamino)-propyl carbodiimide (51 mg., 0.268 mmole, 1 eq.). The mixture was allowed to warm slowly to room temperature and stirred overnight. Aqueous buffer (pH 4, 7 ml., Mallinckrodt) was added and the mixture was stirred for 30 minutes. The product was extracted into ethyl acetate (2×10 ml.), dried MgSO4), and freed of solvent in vacuo. The remaining material was chromatographed on silica gel (Merck, 15 g.) eluting with 3% methanol in dichloromethane containing 0.2% NH4OH to give 176 mg. of [1S-(1R*,2S*,3S*)]-[(1,1-dimethylethoxy)carbonyl]-N-[4-[(butylamino)-sulfonyl]-1-(cyclohexylmethyl)-2,3-dihydroxybutyl]-3-[(phenylmethoxy)methyl]-L-histidinamide. TLC (silica gel; 10% methanol in dichloromethane containing 0.2% NH4OH) Rf =0.59.

Workup

  1. temperatureThe solution was cooled to 0°
  2. additionAqueous buffer (pH 4, 7 ml., Mallinckrodt) was added
  3. stirringthe mixture was stirred for 30 minutes
  4. extractionThe product was extracted into ethyl acetate (2×10 ml.), dried MgSO4), and
  5. customThe remaining material was chromatographed on silica gel (Merck, 15 g.)
  6. washeluting with 3% methanol in dichloromethane containing 0.2% NH4OH
  7. customto give 176 mg

Sources & evidence

ORD record
ord-b038ff03181e4e5d933da4e3a2feace5
Source dataset
uspto-grants-1992_03
Patent number
US05098924

Reaction notes

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