2-chloro-4-phenyl quinazoline

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. 

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... 

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). 

BuOK. (15.4 g, 0.139 mol) was added in portions to 6-chloro-2-(chloromethyl)-4-phenyl-l,2-dihydro-quinazoline 3-oxide (11a 42.2 g, 0.137 mol) in THF (700 mL), cooled in acetone/solid carbon dioxide, and the mixture was stirred for 4.5 h as it warmed to 20 C. It was filtered through Celite, the filtrate was evaporated under reduced pressure and the residue was recrystallized (benzene/hexane) to give the crude aziridinoquinazoline oxide 12a yield 22.Og (57%) mp 135-136.5 C. 

It has been established that the conversion of 2-chloro-4-phenylquinazo-line into 2-amino-4-phenylquinazoline by treatment with potassium amide/liquid ammonia also occurs with ring opening (74RTC227).This was proved by the experimental result that in the 2-amino compound obtained from 2-chloro-4-phenyl[3- N]quinazoline, about 70% of the label is present in the amino group, i.e., formation of 2-[ N-amino]-4-phenylquina-zoline (83) see Scheme 11.36. 

Another approach to the syntheses of quinazolines involves 3-(o-azido-phenyl)isoxazoles (210) which are accessible from a-chloro-Z-azido benzal-doximes (209) and /3-keto esters (R = Ph, = OEt). As shown in Scheme 78, the iminophosphorane resulting from the Staudinger reaction is transformed without isolation by an aza-Wittig reaction into 3,4-disubstituted isoxazolo[4,3-c]quinolines (211) (92MI1). 

Quinazolines take part in the same types of reactions as pyrimidines, but because of their additional benzene ring, the products of these reactions may have the added feature of hindered rotation. An example of this is the synthesis of 2-phenyl-Quinazolinap by Guiry and co-workers <99TA2797>. Suzuki coupling of 4-chloro-2-phenylquinazoline (115) with boronic acids 116 led to 117 (R = OMe). These intermediates were parlayed into phosphinamines 117 (R = PPh2) and then subjected to chiral resolution to produce new chiral phosphinamine ligands for asymmetric catalysis. 

Cyclization of 2-bromomethyl-6-chloro-l-methyl-4-phenyl-l, 2,3,4-tet-rahydro-quinazolines (9) with sodium hydroxide gave the azirino [2,1 -b quinazolines (10) (72BRP1279842). 

Chloro-3,4,7-l 1 b-tetrahydro-2//,6//, 1 lb-phenyl-1, 3-oxazino[3,2-c]-quinazolines (574) were obtained by the reaction of 2-acylamino-5-chlorobenzophenones (573) with 3-aminopropanoI [70YZ629 72GEP-(0)2141616 80PHA256 81CPB2135]. 

The 3-azido-3/f-indoles 3 undergo thermal rearrangement, upon refluxing in dimethylformamide, giving variable yields and ratios of quinazolines 4 and quinoxalines 5, along with the formation of the parent indoles 6. Thus, heating of 3-azido-5-chloro-3-methyl-2-phenyl-3//-indolc for 16 hours in dimethylformamide affords 6-chloro-4-methyl-2-phenylquinazoline (30%), 6-chloro-3-methyl-2-phenylquinoxaline (20%), and a trace of 5-chloro-3-methyl-2-phenyl-l//-indole. ... 

N- [3-chloro-4-[(3-fluorophenyl) methoxy] phenyl] -6- [5- [(2 -methy Isu Ifonylethy lam ino) methy l]fu ran-2-yl] quinazolin-4-amine 4-... 

The half-wave potentials ( 1/2) for 4-unsubstituted-, 4-methyl-, 4-phenyl-, 4,T-pyrrolidinyl-, and 4,4 -pyridyl-2-chloroquinazolines and for 2-unsub-stituted-, 2-methyl-, 2-phenyl-, 2,T-pyrrolidinyl-, and 2,4 -pyridyl-4-chloro-quinazolines were measured in dimethylformamide. The values for the latter series gave a satisfactory correlation with the acidic values of 2-unsubsti-tuted-, 2-methyl-, 2-phenyl-, 2,l -pyrrolidinyl-, and 2,4 -pyridyl-quinazolin-4(3//)-ones measured spectrophotometrically in aqueous solution. ... 

The reverse of the above transformation, i.e., conversion of a quinazoline into an indazole, has been observed. Thus photolysis of 6-chloro-2-methyl-4-phenylquinazoline 1-oxide provided l-acetyl-5-chloro-3-phenylindazole, and most probably proceeded via 7-chloro-2-methyl-5-phenyl-3,l,4-benzo-oxadiazepine because the latter yields the same indazole on photolysis. ... 

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