2-Chloro-4-Bromo-3-Picoline

4-bromo-2-chloropyridine (5 g, 26.19 mmol, 1.0 eq.) was dissolved in 30 ml of dry tetrahydrofuran, and under conditions of -70 °C, slowly added dropwise a freshly prepared lithium diisopropylamide solution (50 ml, 28.8 mmol, 1.1 equiv.). Kept at -70 °C, after reaction for one hour, iodomethane (4.087 g, 28.8 mmol, 1.1 eq). After 50 minutes reaction at low temperature, quenched with saturated sodium bicarbonate solution, the reaction, extracted with ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, and concentrated to give a solid compound 4-bromo-2-chloro-3-methylpyridine (5.22 g, yield: 97.2percent).To a solution of Under nitrogen atmosphere, the compound 402-25 (4.80 g, 23.4 mmol, 1.0 eq.), cyclopentylamine (2.988 g, 35.1 mmol, 1.5 eq.), tris(dibenzylideneacetone) dipalladium (1.07 g, 1.17 mmol, 0.05 eq. ), 4, 5-bis(diphenylphosphino)-9, 9-dimethylxanthene (1.22 g, 2.1 mmol, 0.09 eq.) and cesium carbonate (15.24 g, 46.8 mmol mol, 2.0 eq.) was dissolved in dry in toluene (100 ml), and then the oil bath was heated under reflux for 5 hours. Then the reaction was cooled to room temperature, filtered, and concentrated in vacuo. The resulting residue was purified by column chromatography to give a brown oily compound to the 2-chloro-3-methyl-4-cyclopentylaminopyridine (4.52 g, yield: 91.9%).4-bromo-2-chloropyridine (5 g, 26.19 mmol, 1.0 eq.) was dissolved in 30 ml of dry tetrahydrofuran, and under conditions of -70 C, slowly added dropwise a freshly prepared lithium diisopropylamide solution (50 ml, 28.8 mmol, 1.1 equiv.). Kept at -70 C, after reaction for one hour, iodomethane (4.087 g, 28.8 mmol, 1.1 eq). After 50 minutes reaction at low temperature, quenched with saturated sodium bicarbonate solution, the reaction, extracted with ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, and concentrated to give a solid compound