反应详情

A solution of 2-{(E)-2-[2-((R)-1-tert-butoxycarbonylamino-ethyl)-quinolin-7-yl]-vinyl}-tetrahydro-pyran-2-carboxylic acid (135 mg, 0.3 mmol), N,N-diisopropylethylamine (96 mg, 0.133 mL, 0.75 mmol), 4-dimethylaminopyridine (80 mg, 0.66 mmol) and 2-methyl-6-nitrobenzoic anhydride (193 mg, 0.56 mmol) in dichloromethane (5 mL) was stirred at 0° C. under nitrogen. A solution of (S)-1-[(S)-2-((S)-2-hydroxy-3-methyl-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid 2,2,2-trichloro-ethyl ester (142 mg, 0.33 mmol) in dichloromethane (2 mL) was added and the reaction mixture was stirred at room temperature for 6 h. The reaction mixture was diluted with dichloromethane and the solution was washed with ice-cold saturated sodium hydrogen carbonate solution, water, ice-cold hydrochloric acid (1 M), water 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 3:1 to 1:3 to afford the title compound (44 mg, 17%) as a white solid and as a 1:1 mixture of two diastereoisomers. LCMS (m/z) 840.2, 842.0 [M+H], Tr=3.75 min.

1. washthe solution was washed with ice-cold saturated sodium hydrogen carbonate solution, water, ice-cold hydrochloric acid (1 M), water 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