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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
a   Enamine Ltd., 78 Chervonotkatska str., Kyiv, Ukraine
,
Andrii Hrebonkin
a   Enamine Ltd., 78 Chervonotkatska str., Kyiv, Ukraine
,
Pavlo S. Lebed
a   Enamine Ltd., 78 Chervonotkatska str., Kyiv, Ukraine
b   Taras Shevchenko National University of Kyiv, 60 Volodymyrska str., Kyiv, Ukraine
,
Galyna P. Grabchuk
b   Taras Shevchenko National University of Kyiv, 60 Volodymyrska str., Kyiv, Ukraine
,
Dmitriy M. Volochnyuk∗
a   Enamine Ltd., 78 Chervonotkatska str., Kyiv, Ukraine
b   Taras Shevchenko National University of Kyiv, 60 Volodymyrska str., Kyiv, Ukraine
c   Institute of Organic Chemistry, National Academy of Sciences of Ukraine, 5 Murmanska str., Kyiv, Ukraine
,
Sergey V. Ryabukhin  ∗
a   Enamine Ltd., 78 Chervonotkatska str., Kyiv, Ukraine
b   Taras Shevchenko National University of Kyiv, 60 Volodymyrska str., Kyiv, Ukraine
› Author AffiliationsThe work was funded by Enamine Ltd. and supported by the Ministry of Education and Science of Ukraine (Grant Number 0120U102179).
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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

Supporting Information



Publication History

Received: 21 September 2020

Accepted after revision: 18 January 2021

Accepted Manuscript online:
18 January 2021

Article published online:
08 February 2021

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
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