反应详情

To 3-{5-[4-(6-{2-[5-(2-methoxycarbonylamino-3-methyl-butyryl)-5-aza-spiro[2.4]hept-6-yl]-3H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (60 mg, 0.077 mmol) in dioxanes (2 mL) and MeOH (0.5 mL) was added 4N HCl in dioxanes (160 μL). The suspension was stirred for 2 h then concentrated to afford the HCL salt of the crude amine. To the crude amine in DMF (1 mL) was added N-methylmorpholine (34 μL, 0.31 mmol), 2-methoxycarbonylamino-butyric acid (19 mg, 0.11 mmol) and HATU (35 mg, 0.09 mmol). After stirring for overnight the reaction was quenched with formic acid then purified by reverse phase preparative HPLC (5-45% MeCN—H2O; 0.1% formic acid modifier) to afford the title product (51 mg, 0.062 mmol, 80% yield). LCMS-ESI+: calc'd for C47H55N8O6: 827.4 (M+H+). Found: 827.4 (M+H+).

1. concentrationthen concentrated
2. customto afford the HCL salt of the crude amine
3. stirringAfter stirring for overnight the reaction
4. customwas quenched with formic acid
5. customthen purified by reverse phase preparative HPLC (5-45% MeCN—H2O; 0.1% formic acid modifier)