K. Kobayashi, Kota Yamasaki, H. Hiyoshi
2019
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HETEROCYCLES
Abstract
A convenient method for the preparation of 7-(het)aryl[1,4]oxathiino[2,3-d]pyrimidine derivatives using an easily operated two-step sequence starting from 4,6-dichloro-2-(methylsulfanyl)pyrimidine (DCSMP) have been developed. Thus, the starting material is treated with LDA to generate the 5-lithio derivative, which is allowed to react with sulfur and then phenacyl bromide and its derivatives to give 1-(het)aryl-2-{[4,6-dichloro-2(methylsulfanyl)pyrimidin-5-yl]sulfanyl}ethanones. These pyrimidinyl ketones undergo ring closure upon treatment with triethylamine to provide the corresponding desired products in reasonable overall yields from DCSMP. We have been investigating the utility of 4,6-dichloro-2-(methylsulfanyl)pyrimidine (DCSMP) (1) in the preparation of pyrimidine-fused heterocycles. We recently demonstrated that 5-lithiated DCSMP reacted successively with sulfur and 2-bromoacetonitrile to give 2-{[4,6-dichloro-2-(methylsulfanyl)pyrimidin-5yl]sulfanyl}acetonitrile, which could be transformed into 7-(alkylsulfanyl)[1,4]dithiino[2,3-d]pyrimidine6-carbonitrile derivatives on treatment with carbon disulfide in the presence of two equivalents of sodium hydride followed by addition of alkyl halides. We became interested in utilizing phenacyl bromide and its derivatives in place of 2-bromoacetonitrile and envisaged that the resulting 1-(het)aryl-2{[4,6-dichloro-2-(methylsulfanyl)pyrimidin-5-yl]sulfanyl}ethanones (2) could provide 7(het)aryl[1,4]oxathiino[2,3-d]pyrimidines (3) on treatment with an appropriate base. In the present paper, we wish to demonstrate results of our investigation, which provide a very simple and experimentally convenient method for the preparation of this new heterocyclic system. It may offer the possibility to access compounds of potential biological interest.