2-Propenoic acid, 2-cyano-3-ethoxy-, ethyl ester → 2-Cyano-3-(6-methyl-pyridin-3-ylamino)-acrylic acid ethyl ester

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Reaction Steps

To a solution of 3-amino-6-picoline (ChemPacific, 15.00 g, 138.70 mmol), in toluene (400 mL) was added ethyl(ethoxymethylene)-cyano-acetate (Aldrich, 98%, 35.88 g, 208.00 mol), and the reaction mixture was refluxed for 4 hrs. The reaction mixture was concentrated and the solid was collected by filtration to give 2-cyano-3-(6-methyl-pyridin-3-ylamino)-acrylic acid ethyl ester (21.0 g). The filtrate was concentrated and the residue was then purified by Biotage column, eluting with a gradient of 30-75% AcOEt in nHex to give 2-cyano-3-(6-methyl-pyridin-3-ylamino)-acrylic acid ethyl ester (7.6 g, total yield: 28.6 g, 89.0%) which was used in the next step without further purification.

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