Solid-phase synthesis of 4,8-disubstituted-8,9-dihydropyrazino[2,3-g]quinazolin-7(6H)-ones

Abstract

An approach for the solid-phase synthesis of 4,8-disubstituted-8,9-dihydropyrazino [2,3-g/quinazolin-7(6H)-ones from 4-chloro-7-fluoro-6-nitroquinazoline scaffold is described. A chemoselective reaction of resin-bound arylamines (3) with 4-chloro-7-fluoro-6-nitroquinazoline (8) yielded resin-bound 4-arylamino-7-fluoro-6-nitroquinazolines (4), which were reacted with amino acid methyl esters to afford the corresponding resin-bound compound (5). Following the reduction of nitro group and intramolecular cyclization of 5, resin-bound 4,8-disubstituted-8,9-dihydropyrazino[2,3-g/quinazolin-7(6H)-one (6) was yielded. The desired products (7) were obtained in good yields and purities after cleavage from the resin. ©2007 Wiley Periodicals, Inc.