Solid-phase synthesis of 1,3-disubstituted 2-thioxoquinazoline-4-ones using SNAr reaction

We have developed a solid-phase synthesis of diverse 1,3-disubstituted 2-thioxoquinazoline-4-ones. In this synthesis, the fluorine atom on support-bound 2-fluoro-5-nitrobenzoyl amides was substituted with various primary amines, followed by cyclization with thiocarbonyldiimidazole. Since 1-substitutions can be achieved with primary amines, diverse 1,3-disubstituted 2-thioxoquinazoline-4-ones can be efficiently synthesized using this method. Although solid-phase synthesis of 2-thioxoquinazoline-4-ones using 2-methoxycarbonylphenylisothiocyanate has been reported previously, the introduction of 1-substitutions could not be achieved due to the reactivity of the 2-sulfur atom with alkyl or aryl halide.