Pyrrolo quinoline-5-carboxylates

Indolylaminomethylenemalonate (617) was cyclized to pyrrolo[3,2-/i]quinolinecarboxylate (618) in 54% yield by heating in diphenyl ether for 5 min. The dihydro derivative (619, R = H) failed to cyclize under similar conditions, but its 7V-(4-methylphenylsulfonyl) derivative (619, R = 4-MePhS02) gave the expected pyrrolo[3,2-/i]quinoline carboxylate (620) in 44% yield [75JCS(P 1)2409]. 

Methoxantin coenzyme (PQQ, pyrrolo quinoline quinone, 2,7,9-tricarboxy-lff-pyrrolo-[2,3- /]-quinoline-4,5-dione, 4,5-dihydro-4,5-dioxo-lfl-pyrrolo[2,3 quinoline-2,7,9-tri-carboxylic acid) [72909-34-3] M... 

Besides the permselective properties, the electrocatalytic properties of ECP films can be also used for the amperometric detection of some target molecules. Accordingly, electrodes modified with PPy, polythiophene (PTh), PAni, and their derivatives were found to catalyze the electrochemical oxidation of ascorbic acid [127-129], NADH [115, 116,130], dopamine [128], pyrrolo-quinoline quinone [131] as a coenzyme of some oxidoreductases, and quinone and derivatives [132, 133]. Selectivity exhibited by these materials could be enhanced by the introduction of an appropriate substituent onto the polymer backbone. So, a facilitated electron transfer between cytochrome c and carboxylic acid or carboxylate-substituted PPy [134] or polyindole [135] has been observed. As such an effect was not obtained with unsubstituted polymer films, the cytochrome c-polymer interaction was e lained on the basis of binding between the polymer substituents and the lysine residues on the redox protein. 

N-( 1,3-Dioxoisoindol-4-yl)aminomethylenemalonate (623) was cyclized to pyrrolo[3,4-/i]quinoline-3-carboxylate (624) by heating in Dowtherm A (87MI1). 

The thermal cyclization of N-( 1,3-dioxoisoindol-5-yl)aminomethylene-malonate (821) in boiling Dowtherm A gave pyrrolo[3,4-g]quinoline-3-carboxylate (822) (87MII). 

The cyclization of isopropylidene 1-indolinylmethylenemalonates (1202) was carried out in polyphosphoric acid at 100°C to yield pyrrolo[3,2,l-y]quinoline-2-carboxylic acids (1203) [82BEP891046, 82BEP891537 83JAP(K)90511], Further pyrrolo[3,2,l-(/]quinolinecarboxylic acids were prepared similarly, in 82-86% yields [82BEP891046, 82BEP891537, 82JAP(K)2285]. 

Methyl phenyl- or p-chlorophenylglycinate afforded with 4-chloroquino-line-3-carboxylate a pyrrolo[3,2-c]quinoline derivative 130 [89H(29)899]. Alkyl a-(2-quinolyl)glycinate was transformed into imidazo[l,5-a]quinoline 131 with DMF-DMA, TOF, or DEMA f91JHC1715, 91ZN(B)1110]. 

Hydrogenation of 1,4-diketones 40 over Pt02, Pt (5%) and Pd/C (5%) catalysts afforded a mixture of pyrrolo[l,2-a]quinoline-5-carboxylates 41, [1,2] oxazino[2,3-fl] quinol i ne-6-ca rboxylates 42 and quinoline-4-carboxyl-ate 43 (06JHC1505). When palladium catalyst was applied, 41 formed only a few percent. 

Methylquinazoline with dimethyl acetylenedicarboxylate under reflux for 16 hours affords tetramethyl 8,9-dihydroazepino[l,2-c]quinazoline-9,10,11,12-tetracarboxylate (8, 2.3%). 2,4-Dimethylquinazoline with dimethyl acetylenedicarboxylate under the same reaction conditions gives hexamethyl l,2,5,6-tetrahydroazepino[l,2-c]pyrrolo[l,2-a]quinazoline-l,2,6,7,8,9-hexa-carboxylate (9, 2%) and 3,4-dihydro-l,6-dimethyl-4a//-pyrimido[1.6-a]quinoline-3,4,4a,5-tetracarboxylate (10). 

Similar methodology was employed for the synthesis of methyl-1, 3-dihydro-2H-pyrrolo[3,4- ]quinoline-2-carboxylate 162 in 65% yield and methyl-l,2-dihydro-3H-pyrrolo[3,4-h]quinoline-3-carboxylate 163 in 25% yield from commercial starting materials 160 and 161 (Scheme 31) (07S3319). 

In a 50-mL round-bottomed flask were placed 0.265 g 4-aminoindole (2.0 mmol) and 0.405 mL diethyl ethoxymethylenemalonate (2.0 mmol, d = 1.07) the mixture was heated at 130°C for 3 h. Any unreacted diethyl ethoxymethylenemalonate was removed under vacuum, leaving 0.50 g 2-[( 1//-indol-4-ylamino)methylene]malonic acid diethyl ester as a brown solid, in a yield of 83%, m.p., 122°C (ethanol). Then 0.50 g of the solid diester (1.7 mmol) was added to 50 mL boiling diphenyl ether in portions after 20 min of refluxing, the precipitate formed by cooling was collected by flltration, washed many times with diethyl ether, and recrystallized from ethanol, yielding 0.360 g ethyl 4-oxo-4,7-dihydro-lH-pyrrolo[2,3-/z]quinolin-3-carboxylate, in ayieldof83%, m.p.280°C (dec.), Rf = 0.45 (EtOAc/MeOH, 8 2). 

In a 100-mL round-bottomed flask were placed 0.260 g of the above ester (1.01 mmol) and 30 mL 2 N NaOH the suspension was heated to complete solution and was then refluxed for 6 h, the reaction was monitored by TLC analysis (EtOAc/MeOH, 8 2). After cooling, the reaction mixture was acidified to pH 5 by acetic acid/water (1 2). A brown precipitate formed, which was collected, washed with water, and dried at 60°C, affording 0.185 g 4-oxo-4,7-dihydro-17f-pyrrolo[2,3-A]quinolin-3-carboxylic acid as a crystalline solid, in a yield of 80%, m.p., 320°C (dec.), Rf = 0.71 (EtOAc/MeOH, 8 2). 

C2 6H2 8CIN3O2, Ethyl 7-chloro-2-methyl-9-phenyl-1-(3-dimethylamino)-propyl-1H-pyrrolo[3,2-b]quinoline-3-carboxylate, 42B, 225 C26H32CIN5O7, 5-(N-Benzyl-N-methyliminioprop-2-enyl)-3,7,8,10-tetra-methyl-1,5-dihydroisoalloxazine perchlorate methanol, 43B, 372 C27Hi8N2f 6,6 -Methylenediphenanthridine, 33B, 127 C2 7H2 3NO11, Pentamethy1 11,11a-dihydro-9-oxo-9H,1OH-cyclobuta(4,5)-cyclopenta(3,4)pyrrolo[1,2-a]quinoline-7,8,10,11,11a-pentacarboxy-late, 42B, 226... 

A mixture of 30 g. 2-amino-7-chloro-5-phenyl-3H-l,4-benzodiazepine and excess ethyl acetoacetate heated 3 hrs. at 145-160 -> 9.8 g. ethyl 7-chloro-2-methyl-9-phenyl-lH-pyrrolo[3,2-b]quinoline-3-carboxylate. F. e. s. J. Szmuszkovicz et al., J. Org. Chem. 41, 1743 (1976). 

Ager IR, Barnes AC, Danswan GW, Hairsine PW, Kay DP, Kennewell PD, Matharu SS, Miller P, Robson P, Rowlands DA, Tully WR, Westwood R (1988) Synthesis and oral antiallergic activity of carboxylic acids derived from imidazo[2,l-c][l,4]benzoxazines, imidazo[l,2-tj] quinolines, imidazo[l,2-a]quinoxalines, imidazo[l,2-a]quinoxalinones, pyirolo[l,2-tj]quinox-alinones, pyrrolo[2,3-a]quinoxalinones, and imidazo[2,l-f>]benzothiazoles. J Med Chem 31 (6) 1098-1115. doi 10.1021/jm00401a009... 

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