Triazolo-quinazolines

Base-catalyzed condensation of 2-azidobenzoic acid or its nitrile with active methylene compounds furnished the 4-substituted 1,2,3-triazolo [l,5-a]quinazolines (290) in good yield [66JCS(C)2290 69JCS(D)423 74JCS(P1)534]. 

This ring system (e.g. 293) was prepared from 1,2,4-triazole precursors, such as 3-amino-l,2,4-triazole (292) by condensation with the 2-(N-phenylamino)methylene-l,3-cyclohexanedione (291) (70MI4). Pertinent 

A synthesis comprising one-step formation of the two heterocyclic rings of this system was reported (80HCA1) in which 2-carboxyphenylhydra-zine was cyclocondensed with 297 to give 298. 

In one synthesis [76JAP(K)76100098], l,2,4-triazolo[4,3-a]quinazolines (304) were prepared from 1,2,4-triazole precursors when 2-(l, 2,4-triazol-3-yl)benzophenones (303, LG = OR,SH, or SR) were cyclized with ammonia. 

Finally, the reduced 1,2,4-triazolo[5,1 -fc]quinazolin-9-ones (310) were prepared from 1,2,4-triazole precursors when 3-amino-l,2,4-triazole (309) was cyclocondensed with 2-ethoxycarbonylcyclohexanones (72MI1 890PP163). 

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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). 

Reaetion of l,3-benzoxazin-4-ones (43, 44) or trithioisatoie anhydride (45) with amidrazones (46, 47) or thiosemiearbazide (48) resulted in the formation of 3-(l-amidino)- (49-51) and 3-(l-thioureido)pyrimidines (52) respeetively. Compounds 49-52 underwent thermal intramoleeular ey-elization to the eorresponding l,2,4-triazolo[l,5-c]quinazolines (53-56) [68CB2106 76MI1 80PHA582 83MI1 85H(23)2357] (Seheme 18). 

Tire mesoionie l,2,4-triazolo[l,5-c]quinazolines 59 were obtained upon eyelization of the 4-thioxo-l,3-benzothiazines 57 with thioearbohydra-zine through the intermediate 3-(4-thiosemiearbazido)pyrimidines 58 (86-JHC43) (Seheme 19). 

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... 

Aminolysis of the 5-substituted-2-mercapto-l,3,4-thiadiazolo[3,2-c]-quinazolinium iodides 119 with butylamine afforded the mesoionic 1,3,4-triazolo[l,5-c]quinazolines 120 [77IJC(B)1110] (Scheme 44). 

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). 

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