Beilstein J. Org. Chem.2021,17, 156–165, doi:10.3762/bjoc.17.16
, 60, Avenue Rockefeller, Bioparc, Bioserra 1 Building, 69008 Lyon, France 10.3762/bjoc.17.16 Abstract In our hands, efficient access to the 4-amino-3-carboxamide disubstituted pyridine-2(1H)-one kinase hinge-binder motif proved to be more challenging than anticipated requiring a significant
-azabenzotriazole; hinge-binder; ionic hydrogenation; library; pyridine-2(1H)-one; Introduction
During a recent medicinal chemistry program targeting a kinase to treat skin disorders, we identified the 4-amino-3-carboxamide disubstituted pyridine-2(1H)-one motif (1) as an interesting starting point. Recently, both
goal of creating a rapid, 3-step route requiring a single preparative LC–MS purification at the end of the sequence (Figure 1).
Results and Discussion
Exploration of the C-3 amide vector: formation of the pyridine-2-(1H)-one motif by palladium catalysis
We decided to validate the route by preparing
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Graphical Abstract
Figure 1:
Retrosynthetic disconnection of our privileged kinase scaffold 1.
Beilstein J. Org. Chem.2019,15, 1612–1704, doi:10.3762/bjoc.15.165
]pyridines under microwave irradiation [115]. 1-Butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF4) was used as ionic liquid for this three-component reaction of pyridine-2(1H)-one 70, acetophenone 71 and o-tosylhydroxylamine (72, Scheme 25). The reason behind the use of an ionic liquid as reaction