28657-80-9

Basic information

• Product Name: CINOXACIN
• Synonyms: 1-ETHYL-1,4-DIHYDRO-4-OXO[1,3]DIOXOLO[4,5-G]CINNOLINE-3-CARBOXYLIC ACID;CINOXACIN;TIMTEC-BB SBB003082;1-ethyl-6,7-methylenedioxy-4(1h)-oxocinnoline-3-carboxylicacid;3)dioxolo(4,5-g)cinnoline-3-carboxylicacid,1,4-dihydro-1-ethyl-4-oxo-(;cinobac;1-ethyl-4-oxo-1,4-dihydro-[1,3]dioxolo[4,5-g]cinnoline-3-carboxylic acid;Cinoxacin (200 mg)
• CAS NO: 28657-80-9
• Molecular Formula: C₁₂H₁₀N₂O₅
• Molecular Weight: 262.22
• EINECS: 249-133-8
• Product Categories: Interferes with DNA SynthesisAntibiotics;Quinolones and FluoroquinolonesMore...Close...;A - KAntibiotics;Antibacterial;Antibiotics A to;Antibiotics A-FAntibiotics;Antibiotics by Application;Antineoplastic and Immunosuppressive AntibioticsAntibiotics;Chemical Structure Class;Inhibits an EnzymeAntibiotics;Mechanism of Action;Spectrum of Activity;CINOBAC
• Mol File: 28657-80-9.mol
• Article Data: 1

Chemical Properties

• Melting Point: 261-262° (dec)
• Boiling Point: 405.47°C (rough estimate)
• Flash Point: 266.6°C
• Appearance: /
• Density: 1.3545 (rough estimate)
• Vapor Pressure: 1.61E-11mmHg at 25°C
• Refractive Index: 1.6660 (estimate)
• Storage Temp.: 2-8°C
• Solubility: 1 M NaOH: soluble50mg/mL
• PKA: pKa 5.38(H2O t=25.0 I=0.025) (Uncertain)
• Stability: Hygroscopic
• CAS DataBase Reference: CINOXACIN(CAS DataBase Reference)
• NIST Chemistry Reference: CINOXACIN(28657-80-9)
• EPA Substance Registry System: CINOXACIN(28657-80-9)

Safety Data

• WGK Germany: 2
• RTECS: JI4640000
• Hazardous Substances Data: 28657-80-9(Hazardous Substances Data)

Usage

Originator

Cinobac,Lilly,UK,1979

Uses

Different sources of media describe the Uses of 28657-80-9 differently. You can refer to the following data:
1. antibacterial
2. Cinoxacin is an antibacterial quinolone previously known for its use in the treatment of urinary tract infections.

Definition

ChEBI: A member of the class of cinnolines that is 6,7-methylenedioxycinnolin-4(1H)-one bearing an ethyl group at position 1 and a carboxylic acid group at position 3. An analogue of oxolinic acid, it has similar antibacterial actions. It was formerly used for the treatment of urinary tract infections.

Manufacturing Process

About 23 g (0.095 mol) of 1-ethyl-6,7-methylenedioxy-4(1H)-oxocinnoline-3- carbonitrile were added to a mixture of 200 ml of concentrated hydrochloric acid and 200 ml of acetic acid. The resultant reaction mixture was heated under reflux for 18 hours, The excess acids were removed under vacuum, and the residue was taken up in 150 ml of a 5% sodium bicarbonate solution. The resultant solution was treated with 5 g of charcoal and filtered. The filtrate was made acidic by the addition of hydrochloric acid and the resulting precipitate was removed by filtration. 23 g, representing a yield of 91.6% of 1-ethyl-6,7-methylenedioxy-4(1H)-oxocinnoline-3-carboxylic acid as light tan crystals which melted at 261°C to 262°C with decomposition were recovered.

Brand name

Cinobac (Lilly).

Therapeutic Function

Antibacterial

Antimicrobial activity

This drug is effective with respect to Gram-negative microorganisms and is used for the same indications as nalidixic and oxolinic acids. Synonyms of this drug are cinobactin, nossacin, uronorm, and others.

Pharmaceutical Applications

A cinnoline derivative formulated for oral administration. It is active against most Enterobacteriaceae, but Ps. aeruginosa, Gram-positive bacteria and anaerobes are resistant.It is well-absorbed when given orally. Administration with food reduces the peak concentration by about one-third, but the area under the concentration–time curve (AUC) remains unchanged. Concentrations in prostatic and bladder tissues reach 60% and 80%, respectively, of the simultaneous serum concentrations.It is almost entirely eliminated in the urine, about 40–60% as unchanged drug and the rest as metabolites, most of which have no antibacterial activity. Urinary concentrations of active drug in the first 2 h after administration of a dose is 100–500 mg/L. Elimination is reduced by probenecid and by renal impairment, the half-life rising to about 12 h in endstage renal failure.Adverse reactions that are common to the group are reported in 4–5% of patients; these are primarily gastrointestinal tract disturbances, but rashes occur in up to 3% and CNS disturbances in less than 1%. Use is restricted to uncomplicated urinary tract infection.

Clinical Use

1-Ethyl-1,4-dihydro-4-oxo[1,3]dioxolo[4,5g]cinnoline-3-carboxylic acid (Cinobac) is a close congener (isostere) ofoxolinic acid (no longer marketed in the United States) andhas antibacterial properties similar to those of nalidixic andoxolinic acids. It is recommended for the treatment of urinary tract infectionscaused by strains of Gram-negative bacteria susceptibleto these agents. Early clinical studies indicate that thedrug possesses pharmacokinetic properties superior to thoseof either of its predecessors. Thus, following oral administration,higher urinary concentrations of cinoxacin thanof nalidixic acid or oxolinic acid are achieved. Cinoxacinappears to be more completely absorbed and less proteinbound than nalidixic acid.

Synthesis

Cinoxacin, 1-ethyl-1,4-dihydro-4-oxo[1,3]-dioxolo[4,5-g] cinnolin-3-carboxylic acid (33.2.14), is synthesized by a different scheme starting with 2-amino-4,5-methylendioxyacetophenone (33.2.10), which is synthesized by reducing 4,5-methylendioxy-2-nitroacetophenone with hydrogen over a platinum catalyst. In diazotation conditions, this undergoes spontaneous heterocyclization to 4-hydroxy-6, 7-methylendioxycinnoline (33.2.11) obviously due to the presence of a significant amount of the enol form of acetophenone (33.2.10) under the reaction conditions. The resulting cinnoline (33.2.11) then undergoes bromination by molecular bromine in the presence of potassium acetate, giving 3-bromo-4-hydroxy-6,7-methylendioxycinnoline (32.2.12). Upon reacting this with univalent copper cyanide in dimethylformamide, the bromine atom is replaced with a cyano group, forming the 3-cyano-4-hydroxy-6,7-methylendioxycinnoline (33.2.13). The resulting product is alkylated at the first position by ethyl iodide using sodium hydride as a base, and the cyano group is hydrolyzed to a carboxyl group using a mixture of hydrochloric and acetic acids, giving the desired cinoxacin.

InChI:InChI=1/C12H10N2O5/c1-2-14-7-4-9-8(18-5-19-9)3-6(7)11(15)10(13-14)12(16)17/h3-4H,2,5H2,1H3,(H,16,17)

Synthetic route

ethyl bromide (74-96-4) + 6,7-methylenedioxy-4(1H)-oxo-cinnolin-3-carboxylic acid ethylester (90447-46-4) + Aliquat 336 (5137-55-3) → cinoxacin (28657-80-9)

Conditions	Yield
With sodium hydroxide; potassium carbonate In water; toluene

cinoxacin (28657-80-9) + sodium hexaflorophosphate + ethanol (64-17-5) + [Ru([9]aneS3)(dmso)3](PF6)2 → [Ru([9]aneS3)(dmso-κS)(cin-κ2O,O)](PF6)*EtOH

Conditions	Yield
With sodium methylate In methanol for 2h; Reflux;	92.9%

cinoxacin (28657-80-9) + nickel(II) sulfate heptahydrate + dimethyl sulfoxide (67-68-5) → {Ni(1-ethyl-1,4-dihydro-4-oxo(1,3)dioxolo(4,5-g)cinnoline-3-carboxylate)2(dimethyl sulfoxide)2}*4H2O + {Ni(1-ethyl-1,4-dihydro-4-oxo(1,3)dioxolo(4,5-g)cinnoline-3-carboxylate)2(H2O)2} (151933-03-8)

Conditions	Yield
With NaOH; H2O In dimethyl sulfoxide mixing DMSO soln. of cinoxacin and of the Ni salt, slow addn. of 5 ml of aq. NaOH with stirring, crystn. of Ni(cinoxacinate)2*2H2O after 1 d; filtration, washing (water), drying at 90°C, crystn. of the Ni complex contg. dimethyl sulfoxide ligands after 2-3 months from the remaining soln., filtration, drying at room temp., elem. anal.;	A 10% B 80%

cinoxacin (28657-80-9) + 1,2,3-Benzotriazole (95-14-7) → 3-(1H-benzo[d][1,2,3]triazole-1-carbonyl)-1-ethyl-[1,3]dioxolo[4,5-g]cinnolin-4(1H)-one (1173208-74-6)

Conditions	Yield
Stage #1: 1,2,3-Benzotriazole With thionyl chloride In dichloromethane at 25℃; for 0.5h; Stage #2: cinoxacin In dichloromethane at 25℃; for 2h;	80%

cinoxacin (28657-80-9) + dimethyl sulfoxide (67-68-5) + zinc(II) chloride (7646-85-7) → {Zn(1-ethyl-1,4-dihydro-4-oxo(1,3)dioxolo(4,5-g)cinnoline-3-carboxylate)2}*4H2O + {Zn(1-ethyl-1,4-dihydro-4-oxo(1,3)dioxolo(4,5-g)cinnoline-3-carboxylate)2(dimethyl sulfoxide)2}*4H2O

Conditions	Yield
With NaOH; H2O In dimethyl sulfoxide mixing of a DMSO soln. of cinoxacin and of ZnCl2, addn. of 1 ml of aq. NaOH with stirring, pptn. of Zn(cinoxacinate)2*4H2O after 12-14 d; filtration, washing (water), drying at 90°C, remaining soln. standing at room temp., crystn. of the Zn complex (contg. additionally DMSO ligands) after a few d, filtration, drying at room temp., elem. anal.;	A 75% B 6%

cinoxacin (28657-80-9) → 1-ethyl-5-nitro-4-oxo-1,4-dihydro-[1,3]dioxolo[4,5-g]cinnolin-3-carboxylic acid (1429439-48-4)

Conditions	Yield
With sulfuric acid; potassium nitrate at 0 - 20℃; for 13h; Inert atmosphere;	75%

cinoxacin (28657-80-9) + methanol (67-56-1) → methyl 1-ethyl-6,7-dihydroxy-4-oxo-1,4-dihydrocinnolin-3-carboxylate (1429438-89-0)

Conditions	Yield
Stage #1: cinoxacin With boron tribromide In dichloromethane at -30 - 20℃; for 41h; Inert atmosphere; Stage #2: methanol In dichloromethane at -30 - 20℃; Inert atmosphere;	74.5%

cinoxacin (28657-80-9) → 1-Ethyl-1H-[1,3]dioxolo[4,5-g]cinnolin-4-one (109773-20-8) + 1-Ethyl-3-hydroxy-1H-[1,3]dioxolo[4,5-g]cinnolin-4-one

Conditions	Yield
With oxygen In methanol for 12h; Ambient temperature; Irradiation; in PBS-solution (pH=8); Yields of byproduct given;	A n/a B 62%
With oxygen In methanol for 12h; Mechanism; Product distribution; Ambient temperature; Irradiation; Iin PBS-solution (pH=8);
With oxygen In methanol for 12h; Ambient temperature; Irradiation; in PBS-solution (pH=8); Yields of byproduct given;	A 0.580 mol B n/a

cinoxacin (28657-80-9) + 5'-monomethoxytrityl-protected 5'-amino-5'-deoxythymidine phosphoramidite + dGdCdGdCdA-resin → cinoxacin 5'-amino-5'-deoxydTdGdCdGdCdA

Conditions	Yield
Multistep reaction.;	55%

cinoxacin (28657-80-9) + [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2 (52462-29-0) + water (7732-18-5) + toluene (108-88-3) → chlorido(η6-p-cymene)(cinoxacinato-κ2O,O')ruthenium(II)*water*0.5toluene

Conditions	Yield
With NaOCH3 In methanol; chloroform byproducts: NaCl; addn. of sodium methylate to soln. of ruthenium compd. and sodium nalidixicate in CHCl3/methanol (1/1), refluxing for 6 h; filtration through celite, addn. of toluene, keeping at room temp. with slow evapn. for 3 d, isolation of crystals, washing with hexane, elem. anal.;	55%

cinoxacin (28657-80-9) → 1-ethyl-1,4-dihydro-4-oxo[1,3]dioxolo[4,5-g]cinnoline-3-carbonitrile (28657-79-6)

Conditions	Yield
Stage #1: cinoxacin With polyphosphate ester; ammonia In chloroform at 119 - 123℃; for 24h; Stage #2: With polyphosphate ester at 120℃; for 1h;	21%

cinoxacin (28657-80-9) + aqueous cadmium chloride + dimethyl sulfoxide (67-68-5) → {Cd2(1-ethyl-1,4-dihydro-4-oxo(1,3)dioxolo(4,5-g)cinnoline-3-caboxylate)4(DMSO)2} * 2H2O

Conditions	Yield
With NaOH In dimethyl sulfoxide mixing DMSO solns. of cinoxacin (0.4 mmol) and CdCl2*2.5H2O (0.1 mmol); slow addn. of NaOH (0.1 M) with continuous stirring;; slow evapn. at room temp.; crystn. after 2-3 mo; elem. anal.;;	12%

cinoxacin (28657-80-9) → 5-ethyl-5H-[1,3]dioxolo[4,5-f]indole-6,7-dione (67124-17-8)

Conditions	Yield
In formic acid; water (electrochemical reduction);

cinoxacin (28657-80-9) + 2-mercaptoethylamine hydrochloride (156-57-0) → 1-Ethyl-N-(2-mercaptoethyl)-6,7-methylene-dioxy-4(1H)-oxocinnoline-3-carboxamide (86222-61-9)

Conditions	Yield
With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide

cinoxacin (28657-80-9) → 1-Ethyl-6,7-methylenedioxy-4(1H)-oxocinnoline-3-carboxylic acid, methyl ester (86222-62-0)

Conditions	Yield
With sodium hydrogencarbonate In methanol; water

cinoxacin (28657-80-9) + cobalt(II) perchlorate hexahydrate → sodium tris(1-ethyl-4(1H)-oxo-(1,3)dioxolo(4,5-g)cinnoline-3-carboxylato)cobaltate(II)*10H2O

Conditions	Yield
With sodium hydroxide In water; dimethyl sulfoxide Co(ClO4)2*6H2O mixed with cinoxacin; soln. NaOH added with stirring for1 h; filtered; washed (DMSO); dreid in vac. at 50°C to const. wt.; elem. anal.; powd. XRD; TG-DTA;

cinoxacin (28657-80-9) + copper(II) nitrate trihydrate → bis(1-ethyl-4(1H)-oxo-(1,3)dioxolo(4,5-g)cinnoline-3-carboxylato)copper(II) hydrate

Conditions	Yield
With sodium hydroxide In water; dimethyl sulfoxide cinoxacin mixed with Cu(NO3)2*3H2O; NaOH added with stirring; ppt. filtered; washed (DMSO); dried in vac. at 50°C; elem. anal.; powd. XRD, TG-DTA;

cinoxacin (28657-80-9) + nickel(II) perchlorate hexahydrate → tris(1-ethyl-4(1H)-oxo-(1,3)dioxolo(4,5-g)cinnoline-3-carboxylato)dinickel(II) perchlorate octahydrate

Conditions	Yield
With sodium hydroxide In methanol; water cinoxacin mixed with Ni(ClO4)2*6H2O; NaOH added with stirring; evapn. at room temp. for several d; filtered; washed (methanol); dried in vac. at 50°C; elem. anal.; powd. XRD, TG-DTA;

cinoxacin (28657-80-9) + copper(II) nitrate trihydrate + histamine (51-45-6) → [Cu(cinoxacinate)2] (186689-97-4) + [Cu(histamine)(cinoxacinate)NO3]H2O

Conditions	Yield
With NaOH In ethanol; water addn. of freshly prepared soln. of histamine in ethanol to aq. soln. of copper salt, addn. of an aq. soln. of cinoxacin with NaOH; cooling overnight, filtration, cooling filtrate in refrigerator for 7- 8months; elem. anal.;

cinoxacin (28657-80-9) + copper dichloride → aquachloro(1-ethyl-1,4-dihydro-4-oxo-1,3-dioxolo[4,5-g]cinnoline-3-carboxylato-O(3),O(4))(1-ethyl-1,4-dihydro-4-oxo-1,3-dioxolo[4,5-g]cinnoline-3-carboxylic acid-O(3),O(4))copper(II)

Conditions	Yield
In methanol stoich. amts., warm solvent; pptn. on standing for few d, collection (filtration); single crystals fro mother liquor on slow evapn.;

cinoxacin (28657-80-9) + C119H147N34O53P8Pol → C131H155N36O57P8Pol

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide

cinoxacin (28657-80-9) → 1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-3-(pyrrolidin-1-ylmethyl)cinnolin-4(1H)-one (1429438-94-7)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: boron tribromide / dichloromethane / 41 h / -30 - 20 °C / Inert atmosphere 1.2: -30 - 20 °C / Inert atmosphere 2.1: potassium carbonate; potassium iodide / acetone / Inert atmosphere; Reflux 3.1: potassium hydroxide / methanol; water / 1.5 h / Inert atmosphere; Reflux 3.2: 20 °C / pH 1 / Inert atmosphere 4.1: chloroformic acid ethyl ester; triethylamine / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere 4.2: 2 h / 20 °C / Inert atmosphere 5.1: Dess-Martin periodane / dichloromethane / 1 h / 20 °C / Inert atmosphere 6.1: sodium tris(acetoxy)borohydride; acetic acid / 1,2-dichloro-ethane / 1.5 h / 20 °C / Inert atmosphere View Scheme

cinoxacin (28657-80-9) → C27H25ClN2O6

Conditions

Yield

Multi-step reaction with 4 steps 1.1: boron tribromide / dichloromethane / 41 h / -30 - 20 °C / Inert atmosphere 1.2: -30 - 20 °C / Inert atmosphere 2.1: potassium carbonate; potassium iodide / acetone / Inert atmosphere; Reflux 3.1: potassium hydroxide / methanol; water / 1.5 h / Inert atmosphere; Reflux 3.2: 20 °C / pH 1 / Inert atmosphere 4.1: thionyl chloride / dichloromethane / 1 h / Inert atmosphere; Reflux View Scheme

cinoxacin (28657-80-9) → 1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydrocinnolin-3-carboxamide (1429438-99-2)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: boron tribromide / dichloromethane / 41 h / -30 - 20 °C / Inert atmosphere 1.2: -30 - 20 °C / Inert atmosphere 2.1: potassium carbonate; potassium iodide / acetone / Inert atmosphere; Reflux 3.1: potassium hydroxide / methanol; water / 1.5 h / Inert atmosphere; Reflux 3.2: 20 °C / pH 1 / Inert atmosphere 4.1: thionyl chloride / dichloromethane / 1 h / Inert atmosphere; Reflux 5.1: triethylamine / dichloromethane / 0.5 h / 20 °C / Cooling with ice View Scheme

cinoxacin (28657-80-9) → 1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-3-(piperidin-1-ylmethyl)cinnolin-4(1H)-one (1429439-01-9)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: boron tribromide / dichloromethane / 41 h / -30 - 20 °C / Inert atmosphere 1.2: -30 - 20 °C / Inert atmosphere 2.1: potassium carbonate; potassium iodide / acetone / Inert atmosphere; Reflux 3.1: potassium hydroxide / methanol; water / 1.5 h / Inert atmosphere; Reflux 3.2: 20 °C / pH 1 / Inert atmosphere 4.1: chloroformic acid ethyl ester; triethylamine / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere 4.2: 2 h / 20 °C / Inert atmosphere 5.1: methanesulfonyl chloride; triethylamine / dichloromethane / 2 h / Cooling with ice; Inert atmosphere 5.2: Inert atmosphere View Scheme

cinoxacin (28657-80-9) → 5-amino-1-ethyl-4-oxo-1,4-dihydro-[1,3]dioxolo[4,5-g]cinnolin-3-carboxylic acid (1429439-49-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: sulfuric acid; potassium nitrate / 13 h / 0 - 20 °C / Inert atmosphere 2: hydrogenchloride; palladium on activated charcoal; hydrogen; acetic acid / 5 h / 2585.81 Torr / Inert atmosphere View Scheme

cinoxacin (28657-80-9) → 3-carboxy-1-ethyl-4-oxo-1,4-dihydro-[1,3]dioxolo[4,5-g]cinnolin-5-diazonium chloride (1429439-50-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: sulfuric acid; potassium nitrate / 13 h / 0 - 20 °C / Inert atmosphere 2: hydrogenchloride; palladium on activated charcoal; hydrogen; acetic acid / 5 h / 2585.81 Torr / Inert atmosphere 3: hydrogenchloride; sodium nitrite / water / 5 h / 45 °C / Inert atmosphere View Scheme

cinoxacin (28657-80-9) → 5-chloro-1-ethyl-6,7-dihydroxy-4-oxo-1,4-dihydrocinnolin-3-carboxylic acid (1429439-51-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: sulfuric acid; potassium nitrate / 13 h / 0 - 20 °C / Inert atmosphere 2: hydrogenchloride; palladium on activated charcoal; hydrogen; acetic acid / 5 h / 2585.81 Torr / Inert atmosphere 3: hydrogenchloride; sodium nitrite / water / 5 h / 45 °C / Inert atmosphere 4: sulfuric acid / 20 h / 95 °C / Inert atmosphere View Scheme

Upstream product

• 74-96-4 ethyl bromide 
• 90447-46-4 6,7-methylenedioxy-4(1H)-oxo-cinnolin-3-carboxylic acid ethylester 
• 5137-55-3 Aliquat 336 

Downstream Products

• 1429438-93-6 1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydrocinnolin-3-carbaldehyde 
• 1429438-92-5 1-ethyl-3-(hydroxymethyl)-6,7-bis((4-methoxybenzyl)oxy)cinnolin-4(1H)-one 
• 1429438-91-4 1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydrocinnolin-3-carboxylic acid 
• 1429438-90-3 methyl 1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydrocinnolin-3-carboxylate 
• 1429439-59-7 5-chloro-1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-3-(pyrrolidin-1-ylmethyl)cinnolin-4-(1H)-one 
• 1429439-57-5 5-chloro-1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydrocinnolin-3-carbaldehyde 
• 1429439-56-4 5-chloro-1-ethyl-3-(hydroxymethyl)-6,7-bis((4-methoxybenzyl)oxy)cinnolin-4(1H)-one 
• 1429439-54-2 5-chloro-1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydrocinnolin-3-carboxamide 
• 1429439-53-1 5-chloro-1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydrocinnolin-3-carboxylic acid 
• 1429439-52-0 4-methoxybenzyl 5-chloro-1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydrocinnolin-3-carboxylate 
• 1429439-01-9 1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-3-(piperidin-1-ylmethyl)cinnolin-4(1H)-one 
• 1429438-99-2 1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydrocinnolin-3-carboxamide 
• 1429438-94-7 1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-3-(pyrrolidin-1-ylmethyl)cinnolin-4(1H)-one 
• 28657-79-6 1-ethyl-1,4-dihydro-4-oxo[1,3]dioxolo[4,5-g]cinnoline-3-carbonitrile 

Relevant articles and documents

Method for the production of 1-alkyl-6,7-methylene-dioxy-4(1H)-oxo-cinnolin-3-carboxylic acids

A method is disclosed for production of 1-alkyl-4(1H)-oxo-cinnolin-3-carboxylic acids. Mesoxalic acid dialkylester-3,4-methylenedioxy-phenylhydrazone is saponified using 1 to 1.5 Mol alkali into the corresponding monoalkylester, which is cyclicized with a Friedel-Crafts catalyst in the presence of a carboxylic acid anhydride into 6,7-methylenedioxy-4(1H)-oxo-cinnolin-3-carboxylic acid alkylester, which is alkylated with a C1 -C4 alkyl halogenide in the presence of alkali in a suitable solvent, after which the ester is saponified. Small amounts of byproduct alkylated in the 2-position are removed by brief heating and precipitation from alkaline solution, leaving a pure 1-alkyl product. The product is useful for the treatment of urinary tract infections.