Solid Phase Synthesis of 3,4-Disubstituted-7-carbamoyl-1,2,3,4-tetrahydroquinoxalin-2-ones

The solid phase synthesis of 3,4-disubstituted-7-carbamoyl-1,2,3,4-tetrahydroquinoxalin-2-ones 8 is described. 4-Fluoro-3-nitrobenzoic acid is tethered to a solid support via the acid group. Aromatic substitution of the resin-bound aryl fluoride with an α-amino ester is carried out in the presence of DIEA in DMF. The reduction of the aryl nitro group with SnCl 2 ·H 2 O and subsequent intramolecular cyclization result in the formation of the core quinoxalinone. Selective alkylation at the N-4 position of the quinoxalinone is accomplished with alkyl halides in the presence of K 2 CO 3 . The desired products are cleaved from solid supports and obtained in from 32 to 93% isolated yields.