Solid-phase combinatorial synthesis of 1,4-benzoxazin-3(4H)-one and 1,4-benzothiazin-3(4H)-one derivatives

The first solid-phase synthesis of 1,4-benzothiazin-3(4H)-ones and 1,4-benzoxazin-3(4H)-ones is reported. Alkylation of the immobilized 4-hydroxy-3-nitrobenzamide 2a and 3-nitro-4-sulfanylbenzamide 2b, followed by reduction and cyclization gave 4. Further alkylation and acylation was performed on the amide nitrogen in the presence of sodium hydride followed by TFA cleavage to give the desired 1,4-benzothiazin-3(4H)-ones and 1,4-benzoxazin-3(4H)-ones. (C) 2001 Elsevier Science Ltd. All rights reserved.