反应详情

A solution of 2-{(E)-2-[2-((R)-1-tert-butoxycarbonylamino-ethyl)-quinolin-7-yl]-vinyl}-[1,4]dioxane-2-carboxylic acid (50 mg, 0.1 mmol), [(S)-1-[(S)-2-((S)-2-hydroxy-3-methyl-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid 2,2,2-trichloro-ethyl ester (44 mg, 0.1 mmol), N,N-diisopropylethylamine (32 mg, 0.043 mL, 0.25 mmol), 4-dimethylaminopyridine (6 mg, 0.05 mmol) and 2-methyl-6-nitrobenzoic anhydride (58 mg, 0.17 mmol) in dichloromethane (5 mL) was stirred at room temperature under nitrogen for 18 h. The reaction mixture was diluted with dichloromethane and the solution was washed with ice-cold saturated ammonium chloride solution, ice-cold saturated sodium hydrogen carbonate solution and brine. The organic solution was filtered through a hydrophobic frit and the filtrate was evaporated. The residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 1:1 to 1:3 to afford the title compound (47 mg, 55%) as a white solid and as a 1:1 mixture of diastereoisomers. LCMS (m/z) 842.2/844.0 [M+H], Tr=3.25 and 3.31 min.

1. washthe solution was washed with ice-cold saturated ammonium chloride solution, ice-cold saturated sodium hydrogen carbonate solution and brine
2. filtrationThe organic solution was filtered through a hydrophobic frit
3. customthe filtrate was evaporated
4. customThe residue was purified by silica gel chromatography