4-Quinazolones esters

A quinazolone moiety also provides the nucleus for a highly simplified leukotriene antagonist (compare this compound with verlukast (29-6), discussed earlier in this chapter). Condensation of the anthranilate ester (85-1) with formamide leads to the formation of the quinazolone (85-2). Reaction of the salt from the reaction of this product with a strong base with ethyl 3-bromoacrylate leads to vinylation on nitrogen by what is probably an addition-elimination sequence the product is largely the E isomer (85-3). Saponification then affords tiacrilast (85-4) [95]. 

Most cyclizations of 2,3-diaminopyrimidones (e.g., 68) (04JAP(K)107228) or corresponding quinazolones proceed with the participation of carboxylic acids or their derivatives (esters, anhydrides, chlorides, or orthoesters) as shown in Scheme 18. 

Noncyclizcd or saturated intermediates (69, 70) can frequently be found. Cyclizations of quinazolones (e.g., 71a, b) by means of urea (85IJC(B)873) or malonic ester (97BCJ2209) yield triazoloquinazolones 72 and 73, respectively, functionalized at C-2. 

IA with acylhydrazines (156) yields 157, which condenses with ortho esters or aldehydes to the quinazolones 158.197,198 Sulfuric acid cyclizes N-acetyl-iV-methylhydrazine (156) to the quinazolone 159.197 Polyphosphoric... 

Reaction of the enamine-ester 513 with guanidine in boiling ethanol afforded the quinazolone 517. Hydrogenation of which gave the dihydro derivative 518 (92JHC1375) (Scheme 111). 

Cyclocondensation of 2-(acylmethyl)pyridines with alkoxymethylenemalonic esters or with the corresponding nitro compounds )delds derivatives of the 1-quinazolone 21. 

The amino amides 195 were obtained from isatoic or 6-iodoisatoic anhydrides and the esters of amino acids. They were converted by the action of aromatic aldehydes or acetone into derivatives of dihydro-4-quinazolone 196 (ethanol, piperidine, boiling for 1 h, or cone, hydrochloric acid, boiling for 6 h [117] toluene, toluene sulfonic acid, boiling for 0.5 h, [118]). 

On the other hand, nitriles are widely used as intermediates in the synthesis of many types of heterocycles [7] and other compounds of interest in medicinal chemistry, for example, 3,4-dihydroisoquinolines [8], imidazoles [9], indoles [10], lactim ethers [11], napthyridines [12], pyridones [13], pyridopyrimidi-nes [14], pyrimidines [15], quinazolines [16], quinazolones [17], quinolines [18], sydnones [19], 1,2,4,5-tetrazines [20], tetrazoles [21,22], 1,2,4-triazoles [20], N-substituted amides [23], amidines [24] and basic esters [25]. 

Quinazolone-2-carboxylic acid esters from o-aminocarboxylic acid amides... 

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