Zhang Yandong, Yao Chao, Houghten Richard A, Yu Yongping
College of Pharmaceutical Science, Zhejiang University, Zijin Campus, Hangzhou 310058, People's Republic of China.
Biopolymers. 2008;90(3):439-43. doi: 10.1002/bip.20842.
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.
描述了一种从4-氯-7-氟-6-硝基喹唑啉骨架固相合成4,8-二取代-8,9-二氢吡嗪并[2,3-g]喹唑啉-7(6H)-酮的方法。树脂结合的芳基胺(3)与4-氯-7-氟-6-硝基喹唑啉(8)发生化学选择性反应，得到树脂结合的4-芳基氨基-7-氟-6-硝基喹唑啉(4)，其与氨基酸甲酯反应得到相应的树脂结合化合物(5)。在还原硝基并使5进行分子内环化后，得到树脂结合的4,8-二取代-8,9-二氢吡嗪并[2,3-g]喹唑啉-7(6H)-酮(6)。从树脂上裂解后，以良好的产率和纯度得到所需产物(7)。
