反应详情

To a suspension of 1-{3-[1-(5,7-difluoro-quinolin-6-yl)-ethyl]-[1,2,4]triazolo[4,3-b]pyridazin-6-yl}-ethanone (4.2 g, 11.9 mmol) in methanol (250 mL) was added 2-(aminooxy)ethanol hydrochloride (intermediate S) (2.70 g, 23.8 mmol). The mixture was stirred at rt overnight. LC-MS showed the reaction was complete. An aqueous 1N NaOH solution was added slowly until pH 8-9. The mixture was concentrated, extracted with EtOAc, washed with water and brine. The organic layer was dried over anhydrous Na2SO4, filtered, concentrated, and purified by gradient column chromatography (EtOAc:hexane=2:1, then 100% EtOAc, and then MeOH:EtOAc=1:12 as eluent) to afford 4.8 g (98%) of the title compound as a white solid. 1H-NMR (400 MHz, DMSO-d6) δ ppm 8.97 (dd, 1H), 8.44 (m, 1H), 8.25 (d, 1H), 7.64-7.70 (m, 2H), 7.59 (dd, 1H), 5.25 (q, 1H), 4.70 (t, 1H), 4.19 (t, 2H), 3.62 (dd, 2H), 2.02 (d, 3H), 1.88 (s, 3H). LCMS (method A): [MH]+=413, tR=5.09 min.

1. concentrationThe mixture was concentrated
2. extractionextracted with EtOAc
3. washwashed with water and brine
4. dry with materialThe organic layer was dried over anhydrous Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. custompurified by gradient column chromatography (EtOAc