1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 70291844, compound

Participants

Reaction Steps

(2R)-2-(tert-Butoxycarbonylmethylamino)-3-(2-napthyl)propionic acid (5.00 g; 15.8 mmole), HOAt (2.35 g; 17 mmole) and EDAC (3.03 g; 15.8 mmole) were added to methylene chloride (200 ml) and stirred for 15 min. [(5S)-5-carbamoyl-5-((2R)-2-methylamino-3-(2-thienyl)propionylamino)pentyl]carbamic acid 2,2,2-trichloroethyl ester (7.01 g; 14.5 mmole) was added and the mixture was stirred overnight. Methylene chloride (200 ml) was added and the organic phase was washed with water (200 ml), an aqueous solution of sodium hydrogensulphate (200 ml), an aqueous solution of sodium hydrogencarbonate (200 ml) and water (200 ml). The organic phase was dried (magnesium sulphate) and the solvent was removed in vacuo. The residue was dissolved in a mixture of trifluoroacetic acid (30 ml) and methylene chloride (70 ml) and stirred for 15 min. Water (150 ml) and sodium hydrogencarbonate were added to neutral pH, the phases were separated and the aqueous phase was extracted with methylene chloride (2×100 ml) and the phases were separated. The combined organic phase were dried (magnesium sulphate) and the solvent was removed in vacuo and the residue was chromatographed on silica using a mixture of aqueous ammonia in water (25%), ethanol and methylene chloride (0.7:9.3:90) as eluent to afford 6.3 g of ((5S)-5-{(2R)-2-[((2R)-2-amino-3-(2-naphthyl)propionyl)methylamino]-3-(2-thienyl)propionylamino}-5-carbamoylpentyl)carbamic acid 2,2,2-trichloroethyl ester.

Provenance & Evidence