Library quinazolin-4 -ones

A one-pot preparation of pyrrolo[l,2-a]quinazoline libraries with three points of diversification by condensation of a-cyano-ketones and 2-hydrazino-benzoic acids has been developed by Hulme and coworkers (Scheme 6.252) [439]. The protocol simply involved heating a solution of equimolar amounts of the two building blocks in acetic acid at 150 °C for 5 min. In many cases, the final products precipitated directly from the reaction mixture. In such cases, simple washing with diethyl ether yielded the products in >95% purity. A 63-member library was prepared by employing seven a-cyano-ketones and nine 2-hydrazino-benzoic acids. 

Polystyrene grafted SynPhase Lanterns were used by Makino et al.33 at Ajinomoto to synthesize a diverse quinazoline-2-thioxo-4-one library. Lanterns functionalized with long-chain HMP (hydroxymethylphenoxyvaleric amide) linker were coupled with nitrophenols by the action of DIC/ HOAt/DMAP to give nitrobenzenes 14 (Scheme 6). The nitro group was... 

Anthranilic acids and derivatives are often used as starting materials for the preparation of quinazolinones. For example, Drizin and co-workers applied this strategy to build a library of quinazolinones in the search for selective aiA subtype antagonists. Anlhranilate esters 65 reacted with isocyanates to generate quinazolin-2,4-diones 66 <01JMC1971>. Similarly, quinazolin-4-ones 69 were synthesized by first converting 67 to 68 followed by cyclization with an isocyanate under acidic conditions. 

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