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An Efficient Solid-Phase Synthesis of Quinazoline Derivatives
Y. Zhang, C. Xu, R. A. Houghten, Y. Yu*
Zhejiang University and Zhejiang Sci-Tech University, Hangzhou, P. R. of China; Torrey Pines Institute for Molecular Studies, San Diego, USA
24 April 2007 (online)
An efficient approach for the solid-phase synthesis of 2,3-disubstituted 8-arylamino-3H-imidazo[4,5-g]quinazolines 7 has been developed. Thus, reductive amination of resin 1 with arylamines 2 in the presence of NaBH3CN gave the resin-bound arylamines 3. The reaction of 3 with 4-chloro-7-fluoro-6-nitroquinazoline, followed by the reaction with alkylamines afforded 7-alkylamino-4-arylaminoquinazolines 5 via intermediate 4. The reduction of the nitro group in 5 with SnCl2×2H2O and subsequent cyclization reaction with aldehydes were accomplished in one pot to afford imidazoquinazolines 6. The polymer support was cleaved with TFA to provide the desired quinazolines 7 in 12-95% yield.