2-Methyl-2-thiopseudourea sulfate → HCID 178418413, compound

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Reaction Steps

Scheme I describes a typical method for preparing the pyrido[2,3-d]pyrimidin-7(8H)-ones and the 7-(8H)-imides, compounds wherein X is O or NH. The synthesis starts by reacting a cyanoacetate such as ethyl ethoxymethylenecyanoacetate with a thiopseudourea such as 2-methyl-2-thiopseudourea sulfate to provide 5-cyano-4-hydroxy-2-(methylsulfanyl)pyrimidine. This reaction is described more fully in Helv. Chim. Acta., 42:763-772 (1959). The 4-hydroxypyrimidine is next reacted with a halogenating agent such as phosphorous oxychloride or thionyl chloride to provide a 4-halo pyrimidine, for example, 5-cyano-4-chloro-2-(methylsulfanyl)pyrimidine. The halopyrimidine next is reacted with an amine R2NH2 to provide a 5-cyano-4-substituted amino-2-(methylsulfanyl)pyrimidine. The amine utilized can have R2 be the group desired in the final product, for example, alkyl such as methyl, or R2 can be a group that can be later removed, for example, benzyl or the like, to generate compounds wherein R2 is hydrogen. Compounds where R2 is hydrogen can be alkylated and acylated by standard methods.

Provenance & Evidence