2-Methyl-2-thiopseudourea → 2-(Methylsulfanyl)pyrimidine-4-carboxylic acid
Reaction equation
O=[C:2]([CH3:8])[C:3](=O)[C:4]([OH:6])=[O:5].CC[O-].[Na+].[CH3:13][S:14][C:15](=[NH:17])[NH2:16]>>[CH3:13][S:14][C:15]1[N:17]=[C:3]([C:4]([OH:6])=[O:5])[CH:2]=[CH:8][N:16]=1Participants
4
Procedure
In step a of scheme 1, reaction of the ketone with diethyl oxalacetate in the presence of a base, such as sodium ethoxide, and an organic solvent such as ethanol, provides the dioxobutanoic acid. Refluxing the dioxobutanoic acid, in step b, in the presence of a base, such as EtONa, and 2-methylisothiourea followed by and organic extraction and acid wash provides the 2-(methylthio)pyrimidine-4-carboxylic acid. In step c, the carboxylic acid is converted to the amide using standard amine coupling methodologies, such as with PyBOP or EDC, in the presence of the appropriate amine, e.g., NHRcRd. In step d, oxidation of the thiol with an oxidizing agent such as m-CPBA or H2O2 in CH3CO2H provides the sulfinyl or sulfonyl compound. In step e, reaction of the sulfinyl or sulfonyl compound with the appropriate amine, HNRaRb, in an organic solvent such as dioxane provides the compound of formula I.