2.3- Dihydro-1,2,4-triazolo quinolines

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,... 

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). 

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). 

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>. 

Nuvole et al. stated that the cyclization of 974 and its desmethyl derivative gave tautomeric 9-hydroxy-1,2,3-triazolo[4,5-/]quinoline-8-carboxyl-ates (e.g., 975) or 9-oxo-6,9-dihydro-l,2,3-triazolo[4,5-/]quinoline-8-car-boxylates (e.g., 976, depending on the cyclization conditions (in xylene on the action of polyphosphoric acid (PPA) vs. in DMF on the action of PPA and in Dowtherm A under boiling vs. in polyphosphate (89FES609, 89FES619). 

Catalytic reduction followed by condensation with alkoxymethylene derivatives 175 afforded 176. Compound 176i was cyclized to 7-ethoxycarbonyl-6,9-dihydro-6-oxo-2-methyl-2//-triazolo[4,5- ]quinoline 177. The IR spectra of compounds 176 revealed CN group stretching vibrations at 2200 cm and NH stretching bands at 2950-3160 and 3445 cm. The UV spectra of 176 showed absorption bands at 280 and 290nm - very similar to those previously reported for 2-methylbenzotriazole. 

C,6H21CIIN5O2 0.5 H2O, lO Chloro-2 [2-(dimethylamino)ethyl]-2,7-dihydro-7-methyl-3H-1,2,4-triazolo[4,3-d][1,4]benzodiazepine-3,6(5H)-dione methiodide hemihydrate, 45B, 297 ClsH2 BrN03, -)-trans-4-Methyl-1Ob-methoxycarbonyl-1,2,3,4,4a,5,6,-1Ob-octahydrobenzo f)quinoline hydrobromide monohydrate, 44B, 259 Cl 6 2 uNftOg, 3-Carboethoxy-5-methyl-5-formyl-A -pyrazoline aminohe-miacetal dimer, 42B, 219... 

A soln. of crude startg. m. in 97%-hydrazine stirred overnight at room temp. -> 7-chloro-5-phenyl-j-triazolo[4,3-a]quinoline (Y 7%) and 4,5-dihydro-5-hy-droxy analog (Y 47%) which can be quantitatively dehydrated by heating in acetic acid. Total Y of 7-chloro-5-phenyl- -triazolo[4,3-a]quinoline 54%. A. Wal-ser, T. Flynn, and R. I. Fryer, J. Heterocyclic Chem. 12, 717 (1975). 

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