35857-89-7

6-Chloropyridazine-3-carbonitrile is a reactant in the synthesis of spiropiperidine-based stearoyl-CoA desaturase-1 inhibitors.

(1) A mixture of 6-chloropyridazine-3-carboxamide (15 g, 95.5 mmol) and pyridine (22.6 g, 23.1 mL, 286.6 mmol) was suspended in dichloromethane and cooled under argon protection to -30°C. Trifluoroacetic anhydride (TFAA) was added slowly and dropwise with stirring, keeping the temperature in the reaction system below -20°C. The reaction mixture was allowed to react at this temperature for 19.5 h. The reaction mixture was then stirred for 19.5 h. The reaction mixture was then allowed to warm up naturally to room temperature. The reaction mixture was poured into water (500 mL) and washed with water (4 x 500 mL) until the aqueous phase was light yellow. The organic phase was dried with anhydrous magnesium sulfate (MgSO?), filtered through a pad of silica gel (50 mm diameter, 30 mm height) and concentrated under reduced pressure. The resulting solid was purified by medium pressure liquid chromatography (MPLC) with an eluent of 40% dichloromethane/20 equivalents of ethyl acetate/hexane to give 6-chloro-3-pyridazinecarbonitrile as a colorless solid (5.25 g, 59% yield). Mass spectrum (EI+): m/z 139 ([M]+). NMR hydrogen spectrum (250 MHz, CDCl?) δ: 7.71 (d, J = 8 Hz, 1H); 7.83 (d, J = 8 Hz, 1H).

[1] Patent: US5994353, 1999, A
[2] Journal of Medicinal Chemistry, 2007, vol. 50, # 13, p. 3086 - 3100
[3] European Journal of Medicinal Chemistry, 1984, vol. 19, # 2, p. 111 - 117