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Updated: Nov 7, 2025

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
One-Pot Reductive Alkylation of 2,4-Dihydroxy Quinolines and Pyridines
Pratik R Chheda1, David A Kummer2, Rachel T Nishimura1
1Discovery Chemistry, Janssen Research and Development, 3210 Merryfield Row, San Diego, California 92121, United States.
Abstract:
A one-pot, Hantzsch ester-mediated Knoevenagel condensation-reduction reaction has been developed for alkylation of a wide range of substituted 2,4-quinoline diols and 2,4-pyridine diols with aldehydes. The process is operationally simple to perform, scalable, and provides highly useful C-3 alkylated quinoline and pyridine diols in yields of 58-92%. The alkylation products can be converted to 2,4-dihaloquinoline and pyridine substrates for further functionalization.
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