1,2-Dichloroethane → N-(1-Naphthylmethyl)-N-[2(S)-((imidazol-4-ylacetyl)-amino)-3(S)-methylpentyl]-glycyl-methionine methyl ester

Participants

Reaction Steps

4-Imidazoleacetic acid (0.064 g, 0.395 mmol), dissolved in DMF (5 mL) was treated with HOBT (0.053 g, 0.40 mmol), EDC (0.076 g, 0.40 mmol), and N-[2(S)-amino-3-methylpentyl)-N-(1-naphtylmethyl)glycyl-methionine methyl ester hydrochloride (0.175 g, 0.329 mmol). The pH was adjusted to 7.5 with Et3N (0.15 mL, 1.1 mmol) and the mixture was stirred at ambient temperature for 24 h. After concentration, and the mixture was partitioned between EtOAc (20 mL) and saturated NaHCO3 solution (10 mL). The aqueous layer was washed with EtOAc (1×20 mL). The organic layers were combined, washed with brine (1×10 m), dried (Na2SO4), filtered and concentrated to give 0.170 g of crude product. Purification by chromatography (silica gel, eluting with 1 to 3% methanol in methylene chloride) gave 0.080 g of pure product. 1H NMR (CD3OD); δ8.30-8.25 (d, 1H, J=9 Hz), 7.91-7.86 (d, 1H, J=6 Hz), 7.85-7.79 (d, 1H, J=9 Hz), 7.56 (s, 1H), 7.55-7.38 (m, 4H), 6.9 (s, 1H), 4.37-4.27 (m, 1H), 4.23-4.04 (m, 3H), 3.67 (s, 3H), 3.49 (ABq, 2H), 3.25 (ABq, 2H), 2.90-2.70 (m, 2H), 2.21-1.97 (m, 2H), 1.95 (s, 3H), 1.88-1.74 (m, 1H), 1.64-1.46 (m, 2H), 1.44-1.25 (m, 1H), 1.14-0.98 (m, 1H), 0.93-0.77 (m, 6H).

Provenance & Evidence