ethyl 3,4-diaminobenzoate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The quinoxalin-2-one of the present example is prepared with 3,4-Diamino-benzoic acid ethyl ester and (thiophen-2-yl) oxo-acetic acid via the method described in Example 12 to afford 2-Oxo-3-thiophen-2-yl-1,2-dihydro-quinoxaline-6-carboxylic acid ethyl ester.

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Referring to Scheme 11-1, to a solution of the bromide 1 (2.0 g, 4.2 mmol, prepared according to published conditions) in dioxane (60 mL) was added bis(pinacolato)diboron (4.32 g, 17 mmol), Pd(PPh3)4 (0.49 g, 0.42 mmol) and potassium acetate (2.06 g, 21 mmol) under nitrogen atmosphere. The reaction mixture was stirred at 80° C. for 5 h, and then diluted with ethyl acetate (150 mL). The organic phase was washed with H2O (20 mL), dried over sodium sulfate and concentrated in vacuo. The residue was further purified by silica gel column chromatography (haxanes/ethyl acetate=1/4 to 0/1 (v/v)) to give 2 (1.73 g, 79% yield). LC-MS (ESI): m/z 523.3 (M+H)+. The organic phase was washed with H2O (20 mL) dried over sodium sulfate concentrated in vacuo The residue was further purified by silica gel column chromatography (haxanes/ethyl acetate=1/4 to 0/1 (v/v))

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of methyl 3-amino-4-hydroxybenzoate (2.5 g, 15 mmol) and methyl 4-formylbenzoate (2.46 g, 15 mmol) in methanol (75 mL) was stirred at rt overnight. The solvent was evaporated under reduced pressure and the remaining residue was dissolved in dichloromethane (150 mL). DDQ (3.5 g, 15.4 mmol) was added and the reaction mixture was stirred at rt for 1 h. Saturated NaHCO3 (200 mL) was added. The suspension was filtered off, the resulting solid was washed with saturated NaHCO3 (50 mL), water (50 mL), and ethyl acetate (100 mL) and dried in vacuo to give compound 1 (4 g, 86% yield) as yellow solid. The solvent was evaporated under reduced pressure the remaining residue was dissolved in dichloromethane (150 mL) the reaction mixture was stirred at rt for 1 h The suspension was filtered off the resulting solid was washed with saturated NaHCO3 (50 mL), water (50 mL), and ethyl acetate (100 mL) dried in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: One mole (152 g.) of 3,4-diaminobenzoic acid was stirred with 2 liters of ethanol in a Morton flask. Hydrogen chloride gas was passed through the stirred suspension for about 2 hours. As the gas was absorbed, the slurry became gel-like in character. Ethanol (500 ml.) was added to the reaction mixture to disperse the gel. The reaction mixture was refluxed 24 hours. The mixture was filtered and the filtrate was evaporated to dryness in vacuo. The filter cake and the filtrate residue were dissolved in 9 liters of water. The aqueous solution was made basic by the addition of solid sodium carbonate. The product precipitated from the basic solution. The material was filtered and dried to yield 130 grams of ethyl 3,4-diaminobenzoate. As the gas was absorbed Ethanol (500 ml.) was added to the reaction mixture to disperse the gel The reaction mixture was refluxed 24 hours The mixture was filtered the filtrate was evaporated to dryness in vacuo The filter cake and the filtrate residue were dissolved in 9 liters of water The aqueous solution was made basic by the addition of solid sodium carbonate The product precipitated from the basic solution The material was filtered dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Five-percent palladium on carbon (0.50 g) was added to a solution of 4.00 g of ethyl 3-amino-4-nitro-benzoate in 100 ml of methanol, and the mixture was stirred in a hydrogen atmosphere at 50° C. for 16 hours. The solid material was separated through filtration, and the filtrate was concentrated to obtain ethyl 3,4-diaminobenzoate. Twenty milliliters of trifluoroacetic acid were added thereto, and the mixture was stirred at 60° C. for 2 hours. The reaction solution was concentrated, and chloroform was added thereto. The crystals precipitated were separated through filtration, and were dried to give 4.46 g of 5-ethoxycarbonyl-2-trifluoromethylbenzimidazole (157). The solid material was separated through filtration the filtrate was concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Five-percent palladium on carbon (0.50 g) was added to a solution of 4.00 g of ethyl 3-amino-4-nitro-benzoate in 100 ml of methanol, and the mixture was stirred in a hydrogen atmosphere at 50° C. for 16 hours. The solid material was separated through filtration, and the filtrate was concentrated to obtain ethyl 3,4-diaminobenzoate. Twenty milliliters of trifluoroacetic acid were added thereto, and the mixture was stirred at 60° C. for 2 hours. The reaction solution was concentrated, and chloroform was added thereto. The crystals precipitated were separated through filtration, and were dried to give 4.46 g of 5-ethoxycarbonyl-2-trifluoromethylbenzimidazole (157). The solid material was separated through filtration the filtrate was concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The quinoxalin-2-one of the present example is prepared with 3,4-Diamino-benzoic acid ethyl ester and (thiophen-2-yl)oxo-acetic acid via the method described in Example 12 to afford 2-Oxo-3-thiophen-2-yl-1,2-dihydro-quinoxaline-6-carboxylic acid ethyl ester.

反応条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 250-mL round-bottom flask, was placed a solution of ethyl 3,4-diaminobenzoate (5 g, 27.75 mmol, 1.00 equiv) in diethyl oxalate (100 mL). The resulting solution was stirred overnight at 140° C. in an oil bath. Then the resulting solution was cooled to room temperature. The solids were collected by filtration. The solid was dried in an oven under reduced pressure. This resulted in 3.5 g (54%) of ethyl 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylate as a brown solid. Into a 250-mL round-bottom flask, was placed Then the resulting solution was cooled to room temperature The solids were collected by filtration The solid was dried in an oven under reduced pressure This resulted in 3.5 g (54%) of ethyl 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylate as a brown solid

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The quinoxalin-2-one of the present example is prepared with 3,4-Diamino-benzoic acid ethyl ester and (thiophen-2-yl) oxo-acetic acid via the method described in Example 12 to afford 2-Oxo-3-thiophen-2-yl-1,2-dihydro-quinoxaline-6-carboxylic acid ethyl ester.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The quinoxalin-2-one of the present example is prepared with 3,4-Diamino-benzoic acid ethyl ester and (thiophen-2-yl) oxo-acetic acid via the method described in Example 12 to afford 2-Oxo-3-thiophen-2-yl-1,2-dihydro-quinoxaline-6-carboxylic acid ethyl ester.

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Referring to Scheme 11-1, to a solution of the bromide 1 (2.0 g, 4.2 mmol, prepared according to published conditions) in dioxane (60 mL) was added bis(pinacolato)diboron (4.32 g, 17 mmol), Pd(PPh3)4 (0.49 g, 0.42 mmol) and potassium acetate (2.06 g, 21 mmol) under nitrogen atmosphere. The reaction mixture was stirred at 80° C. for 5 h, and then diluted with ethyl acetate (150 mL). The organic phase was washed with H2O (20 mL), dried over sodium sulfate and concentrated in vacuo. The residue was further purified by silica gel column chromatography (haxanes/ethyl acetate=1/4 to 0/1 (v/v)) to give 2 (1.73 g, 79% yield). LC-MS (ESI): m/z 523.3 (M+H)+. The organic phase was washed with H2O (20 mL) dried over sodium sulfate concentrated in vacuo The residue was further purified by silica gel column chromatography (haxanes/ethyl acetate=1/4 to 0/1 (v/v))

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Referring to Scheme 11-1, to a solution of the bromide 1 (2.0 g, 4.2 mmol, prepared according to published conditions) in dioxane (60 mL) was added bis(pinacolato)diboron (4.32 g, 17 mmol), Pd(PPh3)4 (0.49 g, 0.42 mmol) and potassium acetate (2.06 g, 21 mmol) under nitrogen atmosphere. The reaction mixture was stirred at 80° C. for 5 h, and then diluted with ethyl acetate (150 mL). The organic phase was washed with H2O (20 mL), dried over sodium sulfate and concentrated in vacuo. The residue was further purified by silica gel column chromatography (haxanes/ethyl acetate=1/4 to 0/1 (v/v)) to give 2 (1.73 g, 79% yield). LC-MS (ESI): m/z 523.3 (M+H)+. The organic phase was washed with H2O (20 mL) dried over sodium sulfate concentrated in vacuo The residue was further purified by silica gel column chromatography (haxanes/ethyl acetate=1/4 to 0/1 (v/v))