TfO-mediated [4+2]-annulation of anthranils with 2-chloropyridines: enabling access to pyridoquinazolinones and euxylophoricine B

We present an efficient approach for synthesizing pyridoquinazolinones in the presence of triflic anhydride utilizing anthranils and 2-chloropyridines as starting materials. In this process, Tf 2 O initially activates anthranils forming an electrophilic 1-((trifluoromethyl)sulfonyl)benzo[ c ]isoxazol-1-ium species. This species undergoes an in situ annulation reaction with 2-chloropyridines, resulting in therapeutically useful pyridoquinazolinones. The reaction is tolerant to various functional groups, allowing access to a wide range of substituted pyridoquinazolinones in good yields. Furthermore, the synthesis of euxylophoricine B, known to be an antitumor agent, was also achieved. An efficient approach for the synthesis of pyridoquinazolinones in the presence of triflic anhydride utilizing anthranil and 2-chloropyridines as starting materials has been developed.