5-Methylpyrazin-2-amine → N,N-dimethyl-5-(2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yloxy)pyrazine-2-carboxamide

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Reaction Conditions

Reaction Steps

5-methyl-2-aminopyrazine (6.8 g, 63 mmol) was taken up in 70 mL of dimethylether and cooled to 0° C. Dimethyaluminium chloride (131 mmol, 1 M in hexane) was added dropwise. The resulting mixture was warmed up to ambient temperature and stirred for 30 min. Ethyl 4-(5-(dimethylcarbamoyl)pyrazin-2-yloxy)-2-methylbenzofuran-6-carboxylate (I-1d: 10.1 g, 27.3 mmol) in dimethylether (70 mL) was then added to the activated amine solution via canula. The combined solution was heated to reflux overnight. The reaction was cooled on ice and slowly quenched by the dropwise addition of aqueous Rochelle's salt (concentrated, 100 mL). The mixture was stirred for 20 minutes. The mixture was separated. Organic layer was washed with aqueous Rochelle's salt (30 ml), 1N HCl (30 ml), brine (30 ml), dried over sodium sulfate, and concentrated in vacuo. The crude product was purified by column chromatography (silica gel, gradient of ethyl acetate from 50-100% in heptane) to give desired N,N-dimethyl-5-(2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yloxy)pyrazine-2-carboxamide (1: 8.5 gram 72%).

Provenance & Evidence