1.2.4- Triazolo quinolines

Triazolo[4,5-/i]quinoline 143 and triazolo[4,5-/i]quinoline-5-arsonic acid 144 were isolated from mother liquors after reduction and bis-diazotization of 5,7-dinitro-8-(4-toluenesulfone)aminoquinoline in the presence of cupric sulfate with trisodium arsenite (32JCS2196). 

The isomeric triazolo[4,5-/]quinoline 145 was synthetized by the Skraup reaction from 5(6)-aminobenzotriazole (34CB213). 

Oxidation of 5-arylazo-6-aminoquinoline 146 with copper sulfate in pyridine gave the corresponding 2-aryltriazolo[4,5-/]quinolines 147. Condensation of halo-genated nitrobenzenes with triazolo[4,5-/]quinoline 145 yielded the appropriate 2H- and 3//-aryl derivatives. The nitration of 3-phenyl-3//-triazolo[4,5-/]quino-line 147 occurred at position 4 of the phenyl ring (Scheme 46) (73T221). 

When 3-phenyl-3//-triazolo[4,5-/]quinoline was heated at 390 00°C, IH-pyrido[2,3-c]carbazole 149 originated. Its structure could be confirmed by unambiguous synthesis from the 8,9,10,1 l-tetrahydro-7//-pyrido[2,3-c]carbazole (52CJC711). 

Methylbenzotriazole derivatives with an aminoethylene substituent in position 4 also regioselectively produce only the angularly annelated 7-ethoxycarbonyl-6-0X0-6,9-dihydro-2-methyl-2//-triazolo[4,5-/i]quinoline 158. Under alkaline hydrolysis the ester 158 yielded the corresponding acid 159 (90CCC1038, 92FA1001). 

Angularly annelated H- -methy 1-8-ethoxy carbonyl-9-oxo-6,9-dihydrotriazolo [5,4-/]quinolone is formed preferably 164 over the sterically less hindered (9-0X0 group vs 1-methyl group) linearly annelated triazolo[4,5-g]quinoline 165 in a reaction starting from 6-aminoethylene substituted 1-methyIbenzotriazole. Hydrolysis of the cyclization product produced the corresponding acid 166 (Scheme 52) (94CCC1145). 

Esters of 9-oxo-6,9-dihydro-triazolo[4,5-/]quinoline-8-carboxylic acids 176 can be hydrolyzed and decarboxylated to afford the 9-oxo-6,9-dihydrotriazolo[4, 5-/]quinolines 177 (Scheme 55) (87CCC2918, 88CCC1068,90JMC2640). These in turn were aromatized with POCI3 to the appropriate 9-chloroderivatives 178,... 

When reacted with dimethyl acetylenedicarboxylate, the amines produced ben-zotriazolylaminobutendioates 188 accompanied by A-benzotriazolyl substituted 2-pyridones only in the case of 5-amino-2-methyl-2//-benzotriazole, the triazolo-9,10-dihydrobenzo[d]azepine and an unusual cyclization product, triazolo-2-oxindole (convertible into 2-methyltriazolo[4,5-/]carbostyril-9-carboxylate) were formed. The quinolones 189 were aromatized to chloroesters 190 these in turn were hydrolyzed to chloroacids 191 and decarboxylated to 9-chlorotriazolo[4, 5-/]quinolines 192 (Scheme 58) (93H259). The chlorine atom could be replaced with 17 various secondary amines to give the corresponding 9-aminoalkyl(aryl) derivatives 193, some of which exhibit both cell selectivity and tumor growth inhibition activity at concentrations between 10 and 10 " M (95FA47). 

Phenyl-2//-triazolo[4,5-/]quinoline was prepared and used as optical bright-ener, light, and drug stabilizer (86GEP1), whereas 3,5,7-3//-trimethyl-triazolo[4, 5-/]quinoline was identified by gas chromatography/mass spectrometry as a water pollutant of the Shinano River (Japan) (82MI6). 

Methyl-A -(3-methoxyphenyl)-l//-l,2,3-triazolo[5,4-/]quinoline-9-amine was prepared and tested as an immunostimulant (93MI2). 

The 2,3-dihydro-1,2,4-triazolo[4,3-n]quinolines 751 were prepared by the reaetion of 2-ethylhydrazinoquinoline derivatives 750 with aromatie aldehydes (97CH609) (Seheme 130). 

Rearrangement of oxadiazole bearing quinoline 772 gave the triazolo-quinolinyl ketoxime 773 (93H1577) (Seheme 135). 

Chloro-1 -methyl-5-phenyl-s-trizolo[4,3-a]quinoline A stirred mixture of 6triethyl-orthoacetate (0.925 g,0.0057 mol) and xylene (100 ml) was refluxed, under nitrogen, for 2 hours 40 minutes. During this period the ethanol formed in the reaction was removed by distillation through a short,glass helix-packed column. The mixture was concentrated to dryness In vacuo and the residue was crystallized from methanol-ethyl acetate to give 1.28 g of 7-chloro-1-methyl-5-phenyl-s-triazolo[4,3-a]-quinoline (83.9% yield). The analytical sample was crystallized from methylene chloride methanol and had a melting point 252.5°-253.5°C. 

AX(C)1119>, 3-(2 -phenyl-quinolin-4 -yl)-[l,2,4]triazolo[3,4-Albenzothiazole 7 <2002JlST41, 2001MI2>,... 

Though rarely used, this methodology can be illustrated (Equation 28) by reaction at high temperature between 2-aminobenzonitrile (anthranilonitrile) and various cyanoacetic hydrazides of general structure 227 (Ar = Ph, 4-ClC6H4, 4-MeOC6H4). The 4,5-dihydro-[l,2,4]triazolo[4,3-tf]quinolines 228 were obtained in this way <2005SC2481>. 

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