Synthesis of diversely substituted quinazoline-2,4(1H,3H)-diones by cyclization of tert-butyl (2-cyanoaryl)carbamates

Abstract

The synthesis of diversely substituted quinazoline-2,4(1H,3H)-diones by cyclization of tert-butyl (2-cyanoaryl)carbamates using readily accessible Boc protected o-amino nitriles is reported. The reaction proceeds smoothly at room temperature using 1 equiv. of H₂O₂ under basic conditions. This reaction is compatible with a variety of aromatic/heteroaromatic substrates with different functional groups. This strategy can be utilized for the simplified synthesis of goshuyuamide II and an alkaloid isolated from Zanthoxylum arborescens in good yields. This method was also applied to the synthesis of quinazoline-2,4(1H,3H)-diones that are precursors of medicinally important compounds: alfuzosin, terazosin, prazosin, IAAP, doxazosin, FK 366 (zenarestat) and KF31327.