Hydrochloric Acid → [1-(2-{5-[6-(4-{2-[1-(2-Methoxycarbonylamino-2-phenyl-propionyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester

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Reaction Steps

To a solution of 2-{5-[4-(6-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (0.15 g, 0.205 mmol) in CH2Cl2 (2 mL) and MeOH (0.2 mL) was added HCl (in dioxanes, 4 M, 1.0 mL, 4.1 mmol). The solution was stirred at room temperature for 1 h and concentrated to dryness. The resulting solid was dissolved in DMF (2.3 mL). 2-Methoxycarbonylamino-2-phenyl-propionic acid (0.06 g, 0.29 mmol), COMU (0.12 g, 0.27 mmol) and DIPEA (0.2 mL, 1.15 mmol) were added. The reaction was stirred at room temperature for 18 h before HCl (6M, 0.1 mL) was added. The solution was purified by preparative HPLC (Gemini, 15→40% MeCN in H2O (0.1% formic acid)) and lyophilized to provide [1-(2-{5-[6-(4-{2-[1-(2-Methoxycarbonylamino-2-phenyl-propionyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester (0.072 g, 42%). LCMS-ESI+: calc'd for C48H52N8O6: 836.40 (M+); Found: 837.87 (M+H+).

Provenance & Evidence