Acetic Acid → 3-[6-Chloro-2-(ethylamino)-3-pyridinyl]-2-cyano-3-hydroxy-N-methyl-2-propenamide

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Reaction Steps

3.98 g (100 mmol) of 60% sodium hydride in mineral oil are added in small amounts to a solution, cooled to 0-5° C., of 9.80 g (100 mmol) of N-methylcyanoacetamide in 100 ml of anhydrous dimethylformamide. After hydrogen has finished being given off, the mixture is stirred at ambient temperature for 10 minutes and is then again cooled to 0-5° C. A solution of 10.09 g (49.8 mmol) of 2-(aminoethyl)-6-chloronicotinic acid fluoride in 60 ml of dimethylformamide is then added and the medium is stirred at ambient temperature overnight. 2.85 ml (49.8 mmol) of acetic acid are added and the volatile materials are evaporated under reduced pressure. The residue is taken up in water and the product is extracted twice with a dichloromethane:methanol (95:5) mixture and then once with an ethyl acetate:THF (2:1) mixture. The combined organic phases are dried over MgSO4 and then the solvents are evaporated under reduced pressure. 19.0 g of product are obtained, which product is used as is in the following stage.

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