Pyrido cinnoline-8-carboxylate

X-ray investigations on 3,3-bis(tcrt-butoxycarbonyl)-4,5-difluoro-l-methyl-7-oxo-2,3-dihydro-l//,7//-pyrido[3,2,l-(/]cinnoline-8-carboxylate 57 revealed, that 1-methyl group is perpendicular to the plane of the 4-quinolone moiety (96BCJ1371). 

The cyclization of diethyl A[-(4-methylcinnolin-8-yl)aminomethylene-malonate in diphenyl ether at 245°C for 20 min gave pyrido[3,2-/i]cinnoline-8-carboxylate (610) in 31% yield (51JOC1414). 

Methyl 5-fluoro-4-(trifluoromethylsulfonyloxy)-2,3-dihydro-l-methyl-7-0X0-1//,7//-pyrido[3,2,l-iy]cinnoline-8-carboxylate(68,R = Me,R = R = H, R = F, R = Me, R = CF3SO2O) was reacted with 3-tributylstannyl-2-cyclohexen-l-one in the presence of lithium chloride and bis(triphenyl-phosphine)palladium(II) chloride in tetrahydrofuran for 3 days to give a 4-(3-oxo-l-cyclohexen-l-yl)derivative (92EUP470578). 

The 1-hydroxymethyl group of l-hydroxymethyl-7-oxo-l//,7//-pyrido [3,2,l-y]cinnoline-8-carboxylate (81) was O-alkylated by treatment with diethylaminosulfur trichloride and an alcohol in THE. The 4-hydroxy group of 4-hydroxy-7-oxo-l//,7//-pyrido[3,2,l-t7]cinnoline-8-carboxylate... 

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. 

Nonaqueous hydrolysis of pyrido[3,2,l-iy]cinnoline-3,3,8-triearboxylate (86) in TEA gave 8-ester-3-carboxylic acid derivative (87, R = Et)... 

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]. 

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