m-Chloroperbenzoic acid → Pyrido[3,2-d]pyrimidin-2(1H)-one

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Reaction Steps

Substituted dialkyl methylenemalonate of general formula A can be reacted with S-methylisothiouronium sulfate in the presence of appropriate bases in ethanol at reflux to give B. Compounds B can be converted to phenols C by reaction with benzoyl peroxide in the presence of appropriate bases in refluxing carbon tetrachloride or other solvents (for example dioxane). Treatment of compounds C with POCl3 at reflux produces chloropyrimidines D, which are coupled with appropriate anilines in the presence of bases in DMF at a temperature between 50° C. and 120° C. Pyrimidine esters E are converted to amides using a two-step sequence (hydrolysis and amide formation). Reaction of amides G with lithiumhexamethyldisilazane in DMF at a temperature between 100° C. and 140° C. gives pyrido[4,3-d]pyrimidin-5(6H)-one derivatives H. Alternatively, compounds H can be prepared by reaction of compounds G with DMF-DMA in DMF at a temperature between 80° C. and 120° C. followed by refluxing the resulting enamine in acetic acid. Oxidation of the sulfide of compounds H with oxidation reagents (i.e. mCPBA, H2O2-TFA) followed by displacement of the sulfone with appropriate amines and deprotection produce desired pyrimidopyridone analogs I.

Provenance & Evidence