Quinazoline, 3-amino

The rearrangement of l-methyl-2-arainopyrimidine to 2-methyl-aminopyrimidine with alkali has been recently observed in amino-quinazolines. The following rearrangement proceeded in high yields when R was Me, Et, Pr , Ph, and p-MeOC6H4 ... 

Aminoquinazolines have been the subject of considerable investigation and a large number of derivatives have been prepared as potential antimalarials. The secondary and tertiary amino compounds can be prepared from the corresponding chloroquinazolines and the required primary or secondary amines. The reaction depends on the reactivity of the halogen atom, e.g, the 4-chloro atom reacts more readily than the 2-chloro atom in quinazolines and also on the basic strength of the amine used (see 6a). The reaction is... 

Fusion of 4-hydroxyquinazoIine with phosphorus pentasulfide yields 4-mercaptoquinazoline and, similarly, substituted 2,4-dimercapto-quinazolines have been obtained from the corresponding dihydroxy compounds. The greater reactivity of the 4-mercapto as compared with the 2-mercapto group has permitted the preparation of 4-amino-2-mercaptoquinazolines (see 7a). 

Amino- and hydrazino-quinazolines exhibited antibacterial ac-tivity and a patent claim on the in vitro action of 2,4-diamino-quinazolines was rnade. The preparation of thiopegan derivatives as potential antimalarials and antibacterials deserves mention. Complete inhibition of influenza virus in vitro but not in vivo was shown by. 6,8-dichloro-2,4-dihydroxyquinazoline and other cyclic ureas. Activity against trachoma virus was also displayed by several 2-trichloromethylquinazolines. ... 

Quaternary salt formation in 4-quinazoline 3-oxide and its 4-amino and 4-methyl derivatives has been studied by Adachi. These N-oxides, prepared by reaction of the simple quinazoline with hydroxylamine, react with ethyl iodide at N-1, although only in the case of the 4-amino derivative could the ethiodide be purified. The salts are degraded by alkali yielding derivatives of ethylaniline [Eq. (4)]. 

Treatment of 3-amino-4-oxoquinazolines (9) with cyanamide gave the 2-amino-l,2,4-triazolo [l,5-c]quinazolines 11 as a result of cyclodehydration of the intermediate 3-guanidino-4-oxoquinazolines 10 (68CB2106) (Scheme 9). Similarly, reaction of the 3-amino-4-thioxoquinazoline 12 with alkyl or aryl isothiocyanates yielded the mesoionic l,2,4-triazolo[l,5-cjquinazolines 14 (84S881) (Scheme 10). 

A particularly interesting example of this method of synthesis is the cy-clrzation of the 4-amino-3-(2-aminophyenyl)-l,2,4-triazoloes 73 with cyanogen bromide. Primarily, this reaction was applied to synthesize the 6-amino-l,2,4-triazolo[4,3-d]benzodiazepine hydrobromides 74 the obtained products, however, were found to be the l,5-diamino-l,2,4-triazolo-[l,5-c]quinazolin-ium bromides 77. Structure elucidation of 77 was accomplished by direct... 

Aliphatic and aromatic aldehydes condensed with 2-amino-(62BRP898414), 5-amino- (80AJC1147), or 8-amino-l,2,4-triazolo[l,5-cjpyrimidines (68JOC530) to give the related Schiff bases. Treatment of the 2-amino-5-methyl-l,2,4-triazolo[l,5-c]quinazoline 11 with formaldehyde and piperidine in the presence of acetic acid gave the 2-hydroxymethyl-amino-5-(2-piperidinoethyl) derivative 172. Utilization of aromatic aldehydes and piperidine in this reaction gave the 2-arylideneamino-5-styryl derivatives 173 (68CB2106) (Scheme 67). 

Comparison of the UV speetra of 5-amino-2-(2-furyl)-l,2,4-triazolo[l,5-cjquinazolines (196) and its 5-methylamino derivative (197) in neutral, aeidie, and basie media with the speetra of the two tautomerieally looked derivatives—2-(2-furyl)-5-dimethylamino-l,2,4-triazolo[l,5-c]quinazolines (198) (amino-loeked tautomers) and the imino-loeked tautomers 2-(2-furyl)-5-imino-6-methyl-l,2,4-triazolo[l,5-c]quinazolines (199)—indieated that eompounds 196 and 197 are best represented as a mixture of their amino and imino tautomers (88JMC1014) (Seheme 75). 

Cyclocondensation of 2-chloronicotinic acid with 2-amino-5-iodobenzoic acid and methyl 2-amino-4-bromobenzoate in boiling EtOH in the presence of cone. HCl for 18 h gave the 2-iodo and 3-bromo derivatives of 11-0X0-1 l/f-pyrido[2,l-6]quinazoline-6-carboxylic acid (98MIP1, 98MIP2, 99USP5908840, 99USP5914327). 

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). 

Reaction of 2-amino-3-hydroxypyridine and cyclohexanone 433 in boiling AcOH yielded N, 1 -diphenyl-6-hydroxy-3-methyl-11 -0x0-1,2-dihydro-11 //-pyrido[2,l-Z)]quinazoline-2-carboxamide (434) (98MI2, 99USP5908840, 99USP5914327). 

Kinetic studies have been carried out on the displacement reactions of various chloroazanaphthalenes with ethoxide ions and piperi-dine. - 2-Chloroquinoxaline is even more reactive than 2-chloro-quinazoline, thus demonstrating the powerfully electrophilic nature of the -carbon atoms in the quinoxaline nucleus. The ease of displacement of a-chlorine in the quinoxaline series is of preparative value thus, 2-alkoxy-, 2-amino-, - 2-raethylamino-, 2-dimethyl-amino-,2-benzylamino-, 2-mercapto-quinoxalines are all readily prepared from 2-chloroquinoxaline. The anions derived from substituted acetonitriles have also been used to displace chloride ion from 2-chloroquinoxaline, ... 

CN/CC replacements were also observed when the pyrimidine ring is part of a bicyclic system. Reaction of quinazoline with active methylene compounds, containing the cyano group (malonitrile, ethyl cyanoacetate, phenylacetonitrile) gave 2-amino-3-R-quinoline (R = CN, C02Et, Ph) (72CPB1544) (Scheme 12). The reaction has to be carried out in the absence of a base. When base is used, no ring transformation was observed only dimer formation and SnH substitution at C-4 was found. 

Fluoro atom of 2-amino-8,9-difluoro-5-methyl-6,7-dihydro-5//-pyr-ido[3,2,l-y]quinazoline-l,3-dione was replaced by 3-substituted pyrrolidines in the presence of NEt3 in DMSO at 110°C for 18h (01MIP23). 

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