Quinazolin-4-ones, methylation

The DSC curves of methaqualone, 2-methyl-3-o-tolyl-4- 3H)-quinazolin-one, were investigated by Warkentin et al. (292) to determine whether or not... 

Amino-5-chlorobenzophenone and methyl isocyanate, refluxed 15 hr in dichloromethane, gave an excellent yield of 6-chloro-3-methyl-4-phenyl-quinazolin-2-one methyl isothiocyanate in ethanol furnished the corresponding 2-thione.104... 

In many pyrimidine ring syntheses, it is possible or even desirable to isolate an intermediate ripe for ring-closure by the formation of just one bond. For example, ethyl 3-aminocrotonate (502) reacts with methyl isocyanate to give the ureido ester (503) which may be isolated and subsequently converted into 3,6-dimethyluracil (504) by the completion of one bond. However, viewed pragmatically, the whole synthesis involves the formation of two bonds and therefore is so classified. On such criteria, only two pyrimidine/quinazoline syntheses involve the formation of only one bond. 

Quinazolin-2( 1H) -one, 1 -hydro xy-4-methoxy-tautomerism, 3, 106 Quinazolin-2(lH)-one, 4-methyl-synthesis, 3, 109... 

Quinazolin-4-one and its 6-nitro derivative were both shown to exist predominantly in the o-quinonoid form (cf. 96) by ultraviolet spectral comparisons of the parent compound with the 0-methyl derivative and with the two A -methyl analogs, The existence of quinazolin-2- and -4-ones in an oxo-type structure was demonstrated in 1952 by using solid-state infrared data and later confirmed by... 

The reaction of methyl anthranilate and 3-amino-2-chloropyridine in 1,2,4-trichlorobenzene in the presence of KOt-Bu at 50 °C gave 5,1 l-dihydro-6//-pyrido[2,3-Z)]benzodiazepin-6-one and 6-amino-ll//-pyr-ido[2,l-Z)]quinazolin-l 1-one as a by-product (99BMCL3031). 

A series of novel l-substituted-4-phenyl-l,2,3-triazolo(4,3-a)quinazolin-5(4H)-ones 1 were synthesized by the cyclization of 2-hydrazino-3-phenyl-quinazolin-4(3H) 2 with various one carbon donors. The starting material 2-hydrazino-3-phenylquinazolin-4(3H)-one 2, was synthesized from aniline 7 by a novel innovative route. When tested for their in vivo Hi-antihistaminic activity on conscious guinea pigs all the test compounds protected the animals from histamine-induced bronchospasm significantly, whereas the compound l-methyl-4-phenyl-l,2,3-triazolo(4,3-a)quinazolin-5(4H)-one lb (percentage protection 70.7%) was found to be equipotent with the reference standard chlorpheniramine maleate (percentage protection 71%). These compounds show negligible sedation (5%) when compared to the reference standard (26%). Hence they could serve as prototype molecules for future development [1,4,5]. 

The 2-methylthio-3-substituted quinazolin-4(3H)-one 3 was obtained by dissolving 4 in 2% alcoholic sodium hydroxide solution and methylating with dimethylsulfate whilst stirring at room temperature (yield 88%, m.p 124-126 C). The IR spectrum of 3 showed the disappearance of the amino (NH) and thioxo (CS) stretching signals of the starting materials. It showed a peak for carbonyl (CO) stretching at 1680 cm The NMR spectriun of com-... 

Heating 6-[(2-carboxylphenyl)amino]-5-cyano-2-methylpyridine-3-carboxylate in refluxing POCI3 afforded 6-cyano-8-ethoxycarbonyl-9-methyl-ll//-pyrido[2,T3]quinazolin-ll-one, but in PPA at 135-145°C 2-methyl-3-ethoxycarbonyl-4-methyl-5-oxo-5,10-dihydrobenzo(3)-l,8-napthyridine-9-carboxylic acid formed <2004CHE510>. 

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