Premium
Synthetic Strategy Studies for a Concise Access to Functionalized Pyrano[4,3‐ b ]pyridin‐7‐ones: An Entry to Semi‐Rigid Analogs of Antihistamines
Author(s) -
Beghennou Anissa,
Passador Kevin,
Passador Anthony,
Corcé Vincent,
Thorimbert Serge,
Botuha Candice
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202001016
Subject(s) - chemistry , substituent , nitrile , ring (chemistry) , combinatorial chemistry , stereochemistry , organic chemistry
We report short and efficient syntheses of polyfunctionalized 5,8‐dihydro‐7 H ‐pyrano[4,3‐ b ]pyridin‐7‐ones and 1,4‐dihydro‐3 H ‐pyrano[4,3‐ c ]pyridin‐3‐ones which can be considered as new aza analogs of 3‐isochromanones and as promising scaffolds for medicinal chemistry. Depending on the nature of the substituent, three different and complementary synthetic methodologies were used allowing the introduction of significant diversity in the substituent on the lactone ring of the pyranopyridinones. The selective α‐arylation of nitrile (S N Ar) and tert ‐butyl ester enolate (Pd catalyzed) followed by an acidic mediated lactonisation gives access to original C8‐functionalized pyrano[4,3‐ b ]pyridin‐7‐ones and a seleno‐mediated cyclization to C1‐functionalized pyrano[4,3‐ c ]pyridin‐3‐ones. We have also applied the outlined synthetic methodologies to the preparation of potential semi‐rigid analogs of antihistamines.