Solid-phase synthesis of 4,8-disubstituted-8,9-dihydropyrazino[2,3-g]quinazolin-7(6H)-ones.
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.
Zhang
Yandong
Y
College of Pharmaceutical Science, Zhejiang University, Zijin Campus, Hangzhou 310058, People's Republic of China.
Yao
Chao
C
Houghten
Richard A
RA
Yu
Yongping
Y
D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry*; D012015:Reference Standards; D021241:Spectrometry, Mass, Electrospray Ionization
D011799:Quinazolines