反应详情

温度

90 °C

(R)-(1-{[1-(9-aminononyl)piperidin-4-yl]methyl}-1H-1,2,4-triazol-3-yl)(cyclohexyl) phenylmethanol (Preparation 6, 350 mg, 0.706 mg), 8-(benzyloxy)-5-[(1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl]quinolin-2(1H)-one (WO200509286, 345 mg, 0.706 mmol) and sodium hydrogen carbonate (88.9 mg, 1.06 mmol) were combined in acetonitrile (7 mL). After stirring at 90° C. for 72 hours the solvent was removed in vacuo and residue partitioned between dichloromethane (50 ml) and saturated aqueous sodium bicarbonate solution (50 mL). The organic layer was separated, dried over magnesium sulphate, filtered and the solvent removed in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (99:1:0.1 to 95:5:0.5 by volume) to furnish the title compound as a clear glass, in 37% yield, 240 mg (contains 10% of other triazole regio-isomer).

1. customwas removed in vacuo and residue
2. custompartitioned between dichloromethane (50 ml) and saturated aqueous sodium bicarbonate solution (50 mL)
3. customThe organic layer was separated
4. dry with materialdried over magnesium sulphate
5. filtrationfiltered
6. customthe solvent removed in vacuo
7. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane