Triethylamine → HCID 178449997, compound

Participants

Reaction Steps

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.

Provenance & Evidence