A Facile Synthesis of 1,4-Dihydro-2H-pyrimido[4,5-d][1,3]oxazin-2-one Derivatives from 4,6-Dichloro-2-(methylsulfanyl)pyrimidine

A facile three-step sequence has been developed for the preparation of 1,4-dihydro-2H-pyrimido[4,5-d][1,3]oxazin-2-one derivatives from 4,6-dichloro2-(methylsulfanyl)pyrimidine (DCSMP) under mild conditions. Thus, the starting material is treated with LDA to generate the 5-lithiated compound, which is then allowed to react with (het)aromatic and aliphatic aldehydes to give the corresponding 144,6-dichloro-2-(methylsulfanyl)pyrimidin-5-yl]alkan-l-ols. The reaction of these compounds with primary amines in the presence of triethylamine gives 144-(alkylamino)-6-chloro-2-(methylsulfanyepyrimidin-5-yl]alkan-l-ols, of which subjection to successive treatment with an equimolar amount each of sodium hydride and ethyl chloroformate provides the desired 1,4-disubstituted 7-(methylsulfany1)-1,4-dihydro-2H-pyrimido [4,5-d] [1,3]oxazin-2-ones.