Triethylamine → [2-(Benzyloxy)ethyl]-(2-chloro-6-methyl-3-nitropyridin-4-yl)amine

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Reaction Steps

Under a nitrogen atmosphere, triethylamine (40.4 mL, 290 mmol) was added to a solution of 2,4-dichloro-6-methyl-3-nitropyridine (12.0 g, 58.0 mmol), prepared according to the general method of Part A of Example 1 using 2,4-dihydroxy-6-methyl-3-nitropyridine in lieu of 2,4-dihydroxy-5,6-dimethyl-3-nitropyridine, in anhydrous N,N-dimethylformamide (DMF) (200 mL). To the resulting dark brown solution was added 2-(benzyloxy)ethylamine hydrochloride (11.97 g, 63.76 mmol), and the mixture was stirred at room temperature for 23 hours. The volatiles were then removed under reduced pressure, and the residue was mixed with water and ethyl acetate. The organic layer was washed with water (3×200 mL), aqueous sodium bicarbonate (2×200 mL), and brine (3×250 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide a brown oil. The crude product (18.1 g) was purified by column chromatography on silica gel (700 g, eluting with 80:20 hexane:ethyl acetate) to provide an oil which was triturated with 80:20 hexane:ethyl acetate. The resulting crystals were isolated by filtration and dried to provide 4.7 g of [2-(benzyloxy)ethyl]-(2-chloro-6-methyl-3-nitropyridin-4-yl)amine as a yellow solid.

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