7,9-DIMETHOXYCARBONYL-2-ETHOXYCARBONYL-1H-PYRROLO-[2,3-F]QUINOLINE-4,5-DIONE synthesis

Yield:80721-47-7 62%

Reaction Conditions:

with ammonium cerium (IV) nitrate;water in acetonitrile at -5; for 1.58333 h;Cooling with acetone-dry ice;

Steps:

1.I; i

Into a 3-L, 3-neck flask equipped with a mechanical stirrer, a temperature probe, an addition funnel, and a dry ice / acetone bath were placed 5-methoxy-lH pyrrolo[2,3- f]qumoline-2,7,9-tricarboxylic acid 2-ethyl ester 7,9-dimethyl ester (9) (12.09 g, 0.0313 mol) and 600 mL of acetonitrile. The suspension was stirred and cooled to -5 ⁰C. A solution of cerric ammonium nitrate (84.87 g, 0.155 mol) in 120 mL of water was added over a five- minute period. A bright orange solution resulted. Stirring and cooling at -5 ⁰C was continued for 1.5 hours. The reaction mixture was poured into 1380 mL of vigorously-stirred, cold water and stirring was continued for 0.5 hour. The cerrium salts were filtered off and the filtrate was extracted with 3 times with 300 mL of methylene chloride. The methylene chloride solution was dried over 75 g of magnesium sulfate and the solvent removed in vacuo to producel0.15 g of solid. The resulting solid was stirred in a solution of 10 mL of toluene and 10 mL of ethyl acetate. The resulting bright red-orange crystals were collected by filtration and washed with a solution of 3 : 1 ethyl acetate - heptane. The crystals were taken up in 360 mL of methylene chloride and stirred with 5 g of silica gel for one hour. The solution was filtered through Celite 521 and stripped to 7.50 g (62.0%) of the title compound as a red-orange solid.; In step i, 5-methoxy-lH-pyrrolo[2,3-fJquinoline-2,7,9-tricarboxylic acid 2-ethyl ester 7,9-dimethyl ester (9) and acetonitrile were placed in a reaction vessel, cooled and stirred. To this suspension was added a solution of aqueous cerric ammonium nitrate ((NBU)₂Ce(NOs)₆ or CAN) to produce a bright orange solution which was then poured into cold water. The cerrium salts were collected under vacuum and the filtrate was extracted with CH₂Cl₂. The organic extracts were dried over magnesium sulfate (MgSO₄) and concentrated. The resulting residue was taken up in a solution of toluene-ethyl acetate (EtOAc), and the resulting crystals were collected by filtration, washed with EtO Ac-heptane, taken up in CH₂Cl₂ and stirred with silica gel for 1 hour, and then filtered through Celite. The solvent was removed to produce 4,5-dioxo-4,5-dihydro-l H-pyrrolo[2,3-f]quinoline-2,7,9- tricarboxylic acid 2-ethyl ester 7,9-dimethyl ester (10).

References:

WO2006/102642,2006,A1 Location in patent:Page/Page column 10; 17; 1/6