Solid-phase synthesis of small-sized, non-peptidic molecules has emerged as an important drug discovery tool. 1 Synthesis of heterocyclic compounds on solidsupport, in particular, has been focused on because of their applications toward a variety of drug targets. 2 Among various heterocycles, quinazolines are especially attractive pharmacophores because of their wide range of pharmacological activities. 3 As a part of our project to develop an efficient synthetic protocol for quinazo-line analogues from a resin-bound compound with a primary amine, 4 we investigated the synthesis of 1,2,3benzotriazin-4-ones. 1,2,3-Benzotriazin-4-ones are pharmaceutically interesting as they show various biological activities such as sedative, 5 diuretic, 6 anesthetic 7 and antiarthritic 8 activities. Furthermore, the replacement of the pteridyl moiety of folic acid with 1,2,3-benzotriazin-4-ones was achieved, maintaining antitumor activity. 9 Therefore, the development of solid-phase Scheme 1. Solid-phase synthesis of 1,2,3-benzotriazin-4-ones using various 2-aminobenzoic acids.
Abbreviations: N,N%-diisopropylcarbodiimide (DIC); 1-hydroxy-7-azabenzotriazole (HOAt); dichloromethane (DCM); dimethylformamide (DMF); N-methylpyrrolidone (NMP); trifluoroacetic acid (TFA).