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

Abstract

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 SnCl2·H2O 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 K2CO3. The desired products are cleaved from solid supports and obtained in from 32 to 93% isolated yields.