An efficient and practical synthesis of 2,4-substituted pyrido[4,3-d]pyrimidin-5(6H)-ones

[Display omitted] •Efficient synthesis of a versatile pyrido[4,3-d]pyrimidin-5(6H)-one intermediate.•Selective displacement of the 4-methylthio group by various anilines under the acid conditions.•Facile replacement of the 2-methylthio group with diverse amines to biologically significant analogous....

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Bibliographic Details
Published in:Tetrahedron letters 2019-12, Vol.60 (49), p.151312, Article 151312
Main Authors: Tian, Xinrong, Suarez, Dominic P., Li, William Hoi Hong, McSherry, Allison K., Sanchez, Robert M., Moore, Michael L., Axten, Jeffrey M.
Format: Article
Language:English
Subjects:
Anilines
Cyclization
Displacement
Pyrido[4,3-d]pyrimidin-5(6H)-one
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Summary:[Display omitted] •Efficient synthesis of a versatile pyrido[4,3-d]pyrimidin-5(6H)-one intermediate.•Selective displacement of the 4-methylthio group by various anilines under the acid conditions.•Facile replacement of the 2-methylthio group with diverse amines to biologically significant analogous.•BBDM is more functional-group tolerant than DMF-DMA for enamine formation. We describe an efficient synthesis of 2,4-substituted pyrido[4,3-d]pyrimidin-5(6H)-ones, which involves the acid-promoted cyclization of cyano enamine 15 to afford 2,4-bis(methylthio)pyrido[4,3-d]pyrimidin-5(6H)-one 17 as a key intermediate. Selective displacement of the 4-methylthio group by a wide range of anilines followed by oxidation of the 2-methylthio group and subsequent substitution by amines enabled the synthesis of a variety of 2,4-disubstituted pyrido[4,3-d]pyrimidin-5(6H)-ones.
ISSN:0040-4039
1873-3581
DOI:10.1016/j.tetlet.2019.151312