Quinazolone formation anthranilic acid

Condensation of anthrandic acid (77-1) with an iminoether represents another method for preparing quinazolones. The reaction with the iminoether (77-2) from 2-cyano-5-nitrofuran and ethanohc acid can be visualized as proceeding through the formation of the amidine from addition-elimination of anthranilic acid cycliza-tion then affords the observed product (77-3). This is then converted to chloride (77-4) in the usual way. Displacement of the newly introduced chlorine with diethanolamine leads to the formation of nifurquinazol (77-5) [86], one of the antibacterial nitrofmans (see Chapter 8). 

An extension of the Niementowski reaction that has been used for the condensation of anthranilic acids with lactams has been reported by Sastry et al. Addition of phosphorous oxychloride at room temperature to a solution of lactam 46 was followed by addition of anthranilic acid (1). Subsequent stirring at room temperature followed by heating at reflux furnished products 48 in 60-90% yield. The reaction presumably proceeds via formation of 47 followed by condensation with anthranilic acid (1) and cyclodehydration to give 48. Additional examples of phosphorous oxychloride mediated 4-quinazolone syntheses with either anthranilic acid or the corresponding... 

In the first example, nitration of the benzoate (140) with nitric acid affords the nitro derivative. Hydrogenation converts this to the anthranilate (141). In one of the standard conditions for forming quinazolones, that intermediate is then treated with ammonium formate to yield the heterocycle (142). Reaction of 142 with phosphorus oxychloride leads to the corresponding enol chloride (143). Condensation of 143 with m-iodoaniline (144) leads to displacement of chlorine and consequent formation of the aminoquinazoline (145). Reaction with the trimethylsilyl derivative of acetylene in the presence of tetrakis-triphenylphosphine palladium leads to replacement of iodine by the acetylide. Tributylammonium fluoride then removes the silyl protecting group to afford the kinase inhibitor erlotinib (146). ... 

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