Ethyl cinnolin-3-carboxylate

Methoxy-2-(3,3-tetramethylenetriazeno)acetophenone (32) was converted into the sodium salt of ethyl 2-[4-methoxy-2-(3,3-tetramethylenetriaz-l-eno)benzoyl] acetate (33) [NaH, OC(OEt)2, THF, reflux substrate during 8h crude] and thence into ethyl 7-methoxy-4-oxo-l,4-dihydro-3-cinnoline-carboxylate (34) with loss of pyrrolidine (neat F3CCO2H, 0°C, 12 h 83% overall). ... 

Ethyl l,4-dihydro-3-cinnolinecarboxylate (2) gave ethyl 4-bromo-3-cinnoline-carboxylate (3) (substrate, AcOH, then Br2i dropwise, 20°C reflux, 30 min 60% note additional dehydrogenation). " ... 

Ethyl 6,7-difluoro-4-oxo-l,4-dihydro-3-cinnolinecarboxylate (31) gave a separable mixture of ethyl 6,7-difluoro-l-methyl-4-oxo-l,4-dihydro-3-cinnoline-carboxylate (32) and 3-ethoxycarbonyl-6,7-difluoro-2-methylcmnolin-2-ium-4-olate (33) (substrate, K2CO3, Me2NCHO, 80°C, 30 min, then Me2S04] 80°C, 30 min 62% and 9%, respectively) several pairs of isomers were made... 

CN 1 -ethyl-1,4-dihydro-4-oxo[l, 3]dioxolo[4,5-g]cinnoline-3-carboxylic acid... 

Alkylation of ll-mercaptopyrido[l,2-h]cinnolin-6-ium hydroxide inner salts (e.g., 41) with ethyl bromoacetate gave ll-(ethoxycarbonylmethyl(thio derivatives 64 (R = H), which could be hydrolyzed to the ll-(carboxy-methyl)thio derivative or back to the starting compound 41 (74JHC125). Hydrolysis of the ll-bis(methoxycarbonyl)methylene 66 (R = H), and 2-cyano derivatives of 17 (R = H) in boiling HCl afforded 11-methyl and 2-carboxylic acid derivatives, respectively (74JHC125). The 2-nitro derivative of 17 (R = H) was reduced to the 2-amino derivative over Pd/C with NaBH4 in aqueous methanol, and the 2-amino group was acylated with acetic anhydride at 100°C. 

Heating ethyl 5-fluoro-4-[cyano(ethoxycarbonyl)methyl]-2,3-dihydro-l-methyl-7-oxo-l//,7//-pyrido[3,2,l-i7]cinnoline-8-carboxylate (83, R = COOEt) in a mixture of cone. HCl and acetic acid gave the 8-carboxy-4-acetic acid derivative (92EUP470578). The acetic acid group was decarboxylated by heating in boiling ethanol in the presence of NEts to give the 4-methyl derivative. When the 4-[cyano(tert-butoxycarbonyl)methyl]-8-carboxylate 83 (R = COOrBu) was treated with trifluoroacetic acid in methylene chloride at room temperature, the 4-cyanomethyl-8-carboxylate 83 (R = H) was obtained. 

Cyclization of l-[M2,2-bis(fer/)-butyloxycarbonyl)ethyl -A -methyl-amino]-5,6,7,8-tetrafluoro-4-oxoquinoline-3-carboxylates (142, R = F) in the presence of CS2CO3 gave 7-oxopyrido[3,2,l-//]cinnoline-3,3,8-tricarbox-ylates (143) (92EUP470578,92MIP1 95JOC3928 96JCS(CC)61). The cyclization was accompanied by some N—N bond cleavage (5-20%). 

The crystal structure of ethyl 4-(4-rert-butoxycarbonyl-l-piperazinyl)-5-fluoro-2,3-dihydro-l-methyl-2,7-dioxo-l//,7//-pyrido[3,2,l-iy]cinnoline-8-carboxylate (186, R = Et, R = tert-Qu, R = 4-tm-butoxycarbonyl-l-piperazinyl) was determined by means of X-ray diffraction investigation [95T11125]. 

Ethyl l,l-dimethyl-7b-phenyl-la,7b-dihydro-[l//]-cyclopropa[c]cinnoline-lc-carboxylate (192) underwent rearrangement into ethyl 4-isopropenyl-4-phenyl-1,4-dihydro-3-cinnolinecarboxylate (193) (AcOH, reflux, 30 min ... 

Synonyms 1-Ethyl-l,4-dihydro-4-oxo-[l,3]-dioxolo-[4,5-g]-cinnoline-3-carboxylic acid Trade names Cinobac... 

---