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Updated: Oct 25, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Construction of Quinoline-4-carboxylic Acids via DNA-Compatible Doebner Reaction
Gaonan Wang1, Xiaona Zhang1, Zhuo Wen1
1WuXi AppTec, 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai200131, China.
Abstract:
The Doebner reaction is a classical method for the synthesis of quinoline-4-carboxylic acids via the condensation of anilines, aldehydes, and pyruvic acid. However, its application in DNA-encoded library (DEL) technology has been limited due to harsh reaction conditions that degrade the DNA. Herein, we report a DNA-compatible Doebner reaction that proceeds under mild and catalyst-free conditions. This methodology enables the efficient construction of desirable quinoline scaffolds on-DNA with a broad substrate scope for electron-rich and electron-neutral aromatic amines, although electron-deficient aromatic amines generally afford lower conversions. The qPCR and NGS results demonstrate that the reaction conditions preserve DNA amplifiability and sequence fidelity.
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