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0 °C

3-(1-(t-Butyloxycarbonylamino)ethyl)benzoic acid (217 mg, 0.82 mmol) was dissolved in dichloromethane (5 ml) and N,N-dimethylformamide (3 ml). 1-Hydroxy-7-azabenzotriazole (111 mg, 0.82 mmol) was added. The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (157 mg, 0.82 mmol) was added. A solution of (2R)-N-Methyl-2-(methylamino)-3-(2-naphthyl)-N-(2-(2-thienyl)ethyl)propionamide (288 mg, 0.82 mmol) in dichloromethane (3 ml) was added. Ethyldiisopropylamine (0.14 ml, 0.82 mmol) was added. The reaction mixture was stirred for 16 h, while it was warming up to room temperature. It was diluted with ethyl acetate (80 ml) and washed with 10% sodium hydrogen sulfate solution (50 ml). The aqueous phase was extracted with ethyl acetate (2×40 ml). The combined organic layers were washed with saturated sodium hydrogen carbonate solution (50 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silcia (110 g), using ethyl acetate/heptane 1:1 as eluent, to give 479 mg of (1-(3-(N-methyl-N-((1R)-1-(N-methyl-N-(2-(2-thienyl)ethyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamoyl)phenyl)ethyl)carbamic acid tert-butyl ester.

1. temperaturewas warming up to room temperature
2. washwashed with 10% sodium hydrogen sulfate solution (50 ml)
3. extractionThe aqueous phase was extracted with ethyl acetate (2×40 ml)
4. washThe combined organic layers were washed with saturated sodium hydrogen carbonate solution (50 ml)
5. dry with materialdried over magnesium sulfate
6. customThe solvent was removed in vacuo
7. customThe crude product was purified by flash chromatography on silcia (110 g)