Phenyl quinazoline

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]. 

Quite similarly, the reaction product obtained from 2-benzylthio-3-phenylquinazolin-4(3H)-thione and hydrazine should be assigned the structure 2-anilino-3-aminoquinazoline-4(3//)-hydrazone instead of the reported 2-hydrazino-3-phenyl quinazoline-4(3//)hydrazone (Scheme III.23) (70IJC1055). 

The Schmidt reaction of isatin and hydrazoic acid in sulfuric acid gave anthranilamide (81), quinazoline-2,4-dione (79), and 2-(o-amino-phenyl)-quinazolin-4-one (82).297 A similar reaction has been reported... 

The reduction of quinazoline with lithium aluminum hydride gave a mixture of 1,2,3,4-tetrahydroquinazoline and Va-methyl- ,2-toluenediamine. 4-Aryloxy- and 4-alkoxy-quinazolines gave 1,2-di-hydro derivatives, while 2-chloro-4-phenyl- and 4-chloro-2-phenyl-quinazolines gave the corresponding 3,4-dihydroquinolines with reductive loss of halogen.1356... 

AMINODEHYDROXYLATION Diethyl phosphorochloridate. 4-Chloro-2-phenyl-quinazoline. Potassium amide. 

When 8-[(4-Cyanophenyl)imino]-87f-quinazolino[3,2-c][l,2,3]benzotriazine (13) is subjected to decomposition in ethanol, acetic acid, mineral acids, or acetic acid containing iodide, bromide, or azide ions, and 2-naphthol, 4-(4-cyanoanilino)-2-[2-(substituted)phenyl]quinazolines 14 are obtained. ... 

Aminophenyl)-l-methylquinazolin-4(1//)-one rearranges to 2-[(2-methylamino)phenyl]-quinazolin-4(3//)-one on heating under reflux in 18% hydrochloric acid. " ... 

Chlordiazepoxide is prepared by the reaction scheme shown in Figure 6. 6-chloro-2-chloromethyl-4-phenyl-quinazoline 3-oxide is reacted with methylamine which presumably attacks the quinazoline at the 2 position. The nucleophilic attack is followed by enlargement of the ring to yield the 7-chloro-2-(methylamino)-5-phenyl-3H-l,4-benzodiazepine 4-oxide13. A complete review of the chemistry of benzodiazepines presents alternative pathways14. 

The fluorescence and phosphorescence of quinazoline, 6-chloro-4-phenyl-and 6-chloro-l-methyl-4-phenylquinazolin-2(lH)-one were recorded in ethanol containing 1% of concentrated sulfuric acid. The luminescence of these compounds on thin-layer chromatography (TLC) plates saturated with ethanol was reported. 4-Morpholino- and 4-piperidino-6-methoxy-2-phenyl-quinazoline also have luminescent properties, and the ultraviolet fluorescence in the crystals and in hexane or benzene solution was discussed. The time and wavelength resolved emission from quinazoline vapor at low pressures was studied with a pulsed frequency double-dye laser and were compared with those of quinoxaline and cinnoline. ... 

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... 

Niementowski found that no other amide reacted so freely with o-amino-amides as did formamide and that the difficulty increased with each carbon atom added to the acyl group.279 To introduce a C-aryl substituent, it is preferable to heat an oacylamino acid with formamide. Thus, 2-benzamido-benzoic acid, in formamide at 160°C for 3 hr, gave a good yield of 2-phenyl-quinazolin-4-one.293 However, the use of formamide to condense 2-acetamidobenzoic acid resulted in a mixture of two products, one with... 

Transformations of a six-membered ring into a 1,2,3-triazine connectivity are rare. Two isomeric A -amino-4-methyl- (phenyl-) quinazolin-2-ones have been transformed with LTA into 4-methyl- (phenyl-) 1,2,3-benzotriazine in 23-24% yield <1975J(P1)31> see also CHEC(1984). A recent example is the rearrangement of the cyclic nitrosourea 289 under the influence of strong alkali into the unstable tetrahydro-l,2,3-triazine 11 (Equation 129) <1997SC1569> see also <2006BML427>. 

A new synthesis of Lapatinib, an orally active drug for breast cancer, was described. The synthesis involved a palladium-catalyzed regioselective aryla-tion of furfural with 6-bromo-N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl) quinazolin-4-amine (14TL6007). 

A soln. of 26.4 g. estrone in dry diglyme treated with a NaH-mineral oil dispersion, stirred under Ng until Hg-evolution ceases, 25.3 g. 4-chloro-2-phenyl-quinazoline added, and the resulting mixture stirred and refluxed 1.5 hrs. under Ng 50.5 g. crude 3-(2-phenyl-4-quinazolinyloxy)estra-l,3,5(10)-trien-17-one, 25.2 g. suspended in mineral oil, stirred and heated 5 hrs. at 330 35 under Ng 25.0 g. crude 3-(4-oxo-2-phenyl-3(4H)-quinazolinyl)estra-l,3,5(10)-trien-17-one dissolved in abs. ethanol, treated with aq. 40%-NaOH, refluxed 7 hrs., ice-cooled, treated with 12 iV HCl, allowed to stand overnight at room temp., then stirred and refluxed 1.5 hrs. 7.65 g. 3-aminoestra-l,3,5(10)-lrien-17-one. Overall Y 58%. D. F. Morrow and R. M. Hofer, J. Med. Chem. 9, 249 (1966) method s. R. A. Scherrer, 145th ACS Meeting, Sept. 1963, Abstracts 33Q. 

Hydroxylamine hydrodiloride and a slight excess of triethylamine added to a stirred suspension of 5-chloro-2-anilinothiocarboxamidobenzophenone in abs. ethanol, and refluxed 24 hrs. in a water bath -> 6-chloro-2-phenylamino-4-phenyl-quinazoline 3-oxide. Y 87%. F. e. s. A. Metallidis, A. Sotiriadis, and D. Theo-doropoulos, J. Heterocyclic Chem. 12, 359 (1975). 

A mixture of startg. S,S-dimethyl-N-(N-arylbenzimidoyl)sulfimide and enamine (3 eqs.) in tetralin heated under reflux for 14h 4-benzhydryl-6-methyl-2-phenyl-quinazoline. Y 65%. F.e.s. E. Rossi, R. Stradi, Synthesis 1989, 214-5. 

Paneersalvam P, Raj T, Ishar PSM, Singh B, Sharma V, Rather BA (2010) Antieonvulsant aetivity of Sehilf bases of 3-amino-6,8-dibromo-2-phenyl-quinazolin-4(3H)-ones. Indian J Pharm Sei 72 375-378... 

In contrast, diphenylimidoyl isocyanate, PhC=N(Ph)NCO, generated either from the imidoyl chloride and silver cyanate in acetonitrile solution, or, more unusually, by thermolysis of the thiatriazole (224), cyclizes to 2-phenyl-quinazolin-4-one in only poor yield (36%), ° 2-Amino-quinazolines are accessible by the new route outlined in Scheme 54. ... 

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