1-(6-Chloroimidazo(1,2-b)pyridazin-3-yl)ethan-1-one → 1-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-1-(4,6-difluoro-1-methyl-1H-indazol-5-yl)-ethanol

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Reaction Steps

To a solution of 4,6-difluoro-1-methyl-1H-indazole (600 mg, 3.57 mmol) in 20 mL of anhydrous THF at −78° C. was added n-BuLi (1.6M solution in hexane, 2.56 mL, 4.1 mmol). The solution was stirred at this temperature for 1 hour and then a solution of 1-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-ethanone (698 mg, 3.57 mmol) in 10 mL of anhydrous THF was added at −78° C. dropwise. The resulting solution was stirred at this temperature for 3 hours and slowly warmed up to room temperature and stirred overnight. The reaction mixture was quenched with water, extracted with EtOAc for three times. The organic layers were combined and washed with brine, dried over Na2SO4. The crude product was purified with flash chromatography (CH2Cl2:MeOH 95:5) to give the title compound as a yellow oil (530 mg, 41%). 1H-NMR (400 MHz, CDCl3) δ ppm 8.05 (d, 1H), 8.0 (s, 1H), 7.85 (s, 1H), 7.1 (d, 1H), 6.85 (d, 1H), 4.0 (s, 3H), 2.3 (s, 3H). LCMS (method B): [MH]+=363.9, tR=2.15 min.

Provenance & Evidence