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 (intermediate P) (600 mg, 3.57 mmol) in anhydrous THF (20 mL) 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 h and then a solution of 1-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-ethanone (intermediate M) (698 mg, 3.57 mmol) in anhydrous THF (10 mL) was added dropwise. The resulting solution was stirred at this temperature for 3 h and allowed to warm to it slowly and stirred overnight. The reaction mixture was quenched with water, extracted with EtOAc three times. The organic layers were combined and washed with brine, dried over Na2SO4. The crude was purified by flash chromatography (DCM: MeOH=95:5) to give 530 mg (41%) of the title compound as yellow oil. 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