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DOI: 10.1055/s-0039-1707987
Synthesis of Fused Pyridine Carboxylates by Reaction of β-Alkoxyvinyl Glyoxylates with Amino Heterocycles
The work was funded by Enamine Ltd.; O.O.G. was also funded by Ministry of Education and Science of Ukraine (Grant No. 19BF037-03).Publication History
Received: 03 February 2020
Accepted: 15 February 2020
Publication Date:
12 March 2020 (online)
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Abstract
An efficient approach to the preparation of pyridine carboxylates fused with 5- or 6-membered heteroaromatic rings is described. The method relied on the Combes-type condensation of the low-molecular-weight β-alkoxyvinyl glyoxylates as CCC bis-electrophiles and with heteroaromatic amines as NCC binucleophiles. In most experiments, β-alkoxyvinyl glyoxylates without additional substituent at the β position led to the corresponding α-pyridine carboxylates (67–87% yield). In the case of β-methyl-substituted derivative, γ-pyridine carboxylates were obtained in 84–99% yield. It was found that regioselectivity of the condensation could be efficiently tuned by changing conditions, such as solvents and acidic additives (HOAc, DMSO or HCl–1,4-dioxane).
Key words
nitrogen heterocycles - fused pyridine - amino heterocycles - glyoxylates - condensation - regioselectivitySupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0039-1707987.
- Supporting Information
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