Efficient Route for the Synthesis of Diverse Heteroannelated 5-Cyanopyridines

Andrey P. Mityuk; Andrii Hrebonkin; Pavlo S. Lebed; Galyna P. Grabchuk; Dmitriy M. Volochnyuk; Sergey V. Ryabukhin

doi:10.1055/a-1360-9852

Synthesis, Table of Contents

Synthesis 2021; 53(12): 2133-2141
DOI: 10.1055/a-1360-9852

paper

Efficient Route for the Synthesis of Diverse Heteroannelated 5-Cyanopyridines

Andrey P. Mityuk

^aEnamine Ltd., 78 Chervonotkatska str., Kyiv, Ukraine

,

Andrii Hrebonkin

^aEnamine Ltd., 78 Chervonotkatska str., Kyiv, Ukraine

,

Pavlo S. Lebed

^aEnamine Ltd., 78 Chervonotkatska str., Kyiv, Ukraine

^bTaras Shevchenko National University of Kyiv, 60 Volodymyrska str., Kyiv, Ukraine

,

Galyna P. Grabchuk

^bTaras Shevchenko National University of Kyiv, 60 Volodymyrska str., Kyiv, Ukraine

,

Dmitriy M. Volochnyuk∗

^aEnamine Ltd., 78 Chervonotkatska str., Kyiv, Ukraine

^bTaras Shevchenko National University of Kyiv, 60 Volodymyrska str., Kyiv, Ukraine

^cInstitute of Organic Chemistry, National Academy of Sciences of Ukraine, 5 Murmanska str., Kyiv, Ukraine

,

Sergey V. Ryabukhin ∗

^aEnamine Ltd., 78 Chervonotkatska str., Kyiv, Ukraine

^bTaras Shevchenko National University of Kyiv, 60 Volodymyrska str., Kyiv, Ukraine

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Abstract

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Abstract

The new efficient, convenient protocol for the synthesis of heteroannelated 3-cyanopyridines and pyrimidines starting from diverse aminoheterocycles and 3,3-dimethoxy-2-formylpropionitrile sodium salt was elaborated. The advantages and improvements of the procedure compared to previously known methods are shown. The scope and limitations of the method are determined. The impact of the structural features on regioselectivity are discussed. The preparativeness, scalability, and application scope of the elaborated protocol are demonstrated by the synthesis of five heteroannelated 3-cyanopyridines in quantities up to 100 grams.

Key words

aminoheterocycles - heterocyclization - heteroannelated 3-cyanopyridines - heteroannelated 3-cyanopyrimidines - 2-dimethoxy-3-hydroxyacrylonitrile

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References

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