Diethyl Ether → (2-Amino-5-bromopyridin-3-yl)(6-fluoropyridin-2-yl)methanone

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Reaction Steps

To a solution of 2-bromo-6-fluoropyridine (7.5 g, 42.6 mmol) in tetrahydrofuran (50 ml) at 0° C. was added a 2 M solution of isopropylmagnesium chloride in ether (21.3 ml, 42.6 mmol) over a period of 10 minutes. The ice-bath was removed and the reaction mixture was stirred at room temperature for 2 hours. The resulting solution was added dropwise to a solution of 2-amino-5-bromo-N-methoxy-N-methylnicotinamide (3 g, 11.5 mmol) in tetrahydrofuran (40 ml) at room temperature over a period of 30 minutes. The resulting solution was stirred at room temperature for 18 hours. The solution was quenched by addition of an aqueous saturated solution of ammonium chloride at 0° C. and the mixture was stirred at room temperature for 20 minutes. Water was added and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified on silica gel by flash column chromatography (ISCO Companion□, 80 g column, 0-100% EtOAc/Petrol) to give an orange sticky solid which was slurried in ether/MeOH, collected by filtration and dried. The desired compound was obtained as a yellow solid (196 mg, 6% yield).

Provenance & Evidence