反应详情

Methyl chloroformate (15 μL, 0.19 mmol) was added to a solution of 3′-(2-methoxycarbonylamino-3-methyl-butyryl)-4-[4-(4-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-4-yl}-phenylethynyl)-phenyl]-1-(2-trimethylsilanyl-ethoxymethyl)-2′,3′,4′,5′-tetrahydro-1H-[2,4′]biimidazole (97 mg, 0.09 mmol), and 4-methylmorpholine (40 μL, 0.36 mmol) in dichloromethane (3 mL). After 30 minutes the solvent was removed under reduced pressure and azeotroped with toluene. The residue was taken up in dichloromethane (5 mL) and trifluoroacetic acid (5 mL) was added. After 16 hours the volatiles were removed under reduced pressure and the residue was taken up in tetrahydrofuran (4 mL) and methanol (2 mL). An aqueous solution of sodium hydroxide (2 N, 1 mL) was added. After 30 min the organic solvents were removed under reduced pressure and the resulting precipitate was isolated by filtration. The solid was taken up in dimethylformamide (2 mL) and subjected to reverse phase chromatography with an eluent of 0.1% TFA in water and 0.1% TFA in acetonitrile. The product-containing fractions were combined and the solvent was removed by lyophilization to provide 3′-(2-methoxycarbonylamino-3-methyl-butyryl)-4-[4-(4-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-1H-imidazol-4-yl}-phenylethynyl)-phenyl]-2′,3′,4′,5′-tetrahydro-1H-[2,4′]biimidazolyl-1′-carboxylic acid methyl ester (14.1 mg, 0.017 mmol, 10%).

1. customAfter 30 minutes the solvent was removed under reduced pressure
2. customazeotroped with toluene
3. additiontrifluoroacetic acid (5 mL) was added
4. customAfter 16 hours the volatiles were removed under reduced pressure
5. additionAn aqueous solution of sodium hydroxide (2 N, 1 mL) was added
6. customAfter 30 min the organic solvents were removed under reduced pressure
7. customthe resulting precipitate was isolated by filtration
8. customthe solvent was removed by lyophilization