3-(4-chlorophenyl)furan-2,5-dione

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

実験手順: To a suspension of 3-(4-chlorophenyl)-2,5-furandione (10.24 g, 66.9 mmol) in acetic acid (300 mL) was added benzylhydrazine dihydrochloride in one portion (19.6 g, 100 mmol). The reaction mixture was stirred at reflux for 14 h. Analysis by HPLC/MS indicated the reaction was complete. After cooling to room temperature, the resulting white suspension was filtered. The collected solid was washed with EtOAc (20 mL×2), and dried in a 50° C. vacuum oven for 16 h to yield 6.5 g of the desired product as a white solid. The filtrate was concentrated under reduced pressure, and the obtained residue was crystallized in EtOAc to afford additional 1.6 g of the title compound (8.1 g in total, 39% yield). HPLC/MS (method A): retention time=3.29 min, (M+H)+=313.1. 1H NMR (DMSO-d6, 500 MHz): δ 11.62 (s, 1H), 7.65 (d, J=10 Hz, >2H), 7.51 (d, J=10 Hz, 2H), 7.23-7.38 (m, 5H), 7.04 (s, 1H), 5.11 (s, 2H). at reflux for 14 h the resulting white suspension was filtered The collected solid was washed with EtOAc (20 mL×2) dried in a 50° C. vacuum oven for 16 h

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

実験手順: To a suspension of 3-(4-chlorophenyl)-2,5-furandione (10.24 g, 66.9 mmol) in acetic acid (300 mL) was added benzylhydrazine dihydrochloride in one portion (19.6 g, 100 mmol). The reaction mixture was stirred at reflux for 14 h. Analysis by HPLC/MS indicated the reaction was complete. After cooling to room temperature, the resulting white suspension was filtered. The collected solid was washed with EtOAc (20 mL×2), and dried in a 50° C. vacuum oven for 16 h to yield 6.5 g of the desired product as a white solid. The filtrate was concentrated under reduced pressure, and the obtained residue was crystallized in EtOAc to afford additional 1.6 g of the title compound (8.1 g in total, 39% yield). HPLC/MS (method A): retention time=3.29 min, (M+H)+=313.1. 1H NMR (DMSO-d6, 500 MHz): δ 11.62 (s, 1H), 7.65 (d, J=10 Hz, >2H), 7.51 (d, J=10 Hz, 2H), 7.23-7.38 (m, 5H), 7.04 (s, 1H), 5.11 (s, 2H). at reflux for 14 h the resulting white suspension was filtered The collected solid was washed with EtOAc (20 mL×2) dried in a 50° C. vacuum oven for 16 h

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

実験手順: To a suspension of 3-(4-chlorophenyl)-2,5-furandione (10.24 g, 66.9 mmol) in acetic acid (300 mL) was added benzylhydrazine dihydrochloride in one portion (19.6 g, 100 mmol). The reaction mixture was stirred at reflux for 14 h. Analysis by HPLC/MS indicated the reaction was complete. After cooling to room temperature, the resulting white suspension was filtered. The collected solid was washed with EtOAc (20 mL×2), and dried in a 50° C. vacuum oven for 16 h to yield 6.5 g of the desired product as a white solid. The filtrate was concentrated under reduced pressure, and the obtained residue was crystallized in EtOAc to afford additional 1.6 g of the title compound (8.1 g in total, 39% yield). HPLC/MS (method A): retention time=3.29 min, (M+H)+=313.1. 1H NMR (DMSO-d6, 500 MHz): δ 11.62 (s, 1H), 7.65 (d, J=10 Hz, >2H), 7.51 (d, J=10 Hz, 2H), 7.23-7.38 (m, 5H), 7.04 (s, 1H), 5.11 (s, 2H). at reflux for 14 h the resulting white suspension was filtered The collected solid was washed with EtOAc (20 mL×2) dried in a 50° C. vacuum oven for 16 h

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of hydrazine dihydrochloride (5.6 g, 53.3 mmol) in H2O (60 mL) at 120° C. was added 3-(4-chlorophenyl)-2,5-furandione (10 g, 48 mmol) in one portion. After addition, the reaction mixture was stirred at 120° C. for 40 min. After cooling to room temperature, the reaction became a pale yellow suspension. The precipitate was collected by filtration, washed with water (30 mL×3), hexanes (30 mL×3), and dried in a 50° C. vacuum oven for 16 h to afford 8.7 g (81%) of the title compound as a pale yellow solid. LC/MS (method A): retention time=2.57 min, (M+H)+=223. After addition After cooling to room temperature The precipitate was collected by filtration washed with water (30 mL×3), hexanes (30 mL×3) dried in a 50° C. vacuum oven for 16 h

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

実験手順: To a suspension of 3-(4-chlorophenyl)-2,5-furandione (10.24 g, 66.9 mmol) in acetic acid (300 mL) was added benzylhydrazine dihydrochloride in one portion (19.6 g, 100 mmol). The reaction mixture was stirred at reflux for 14 h. Analysis by HPLC/MS indicated the reaction was complete. After cooling to room temperature, the resulting white suspension was filtered. The collected solid was washed with EtOAc (20 mL×2), and dried in a 50° C. vacuum oven for 16 h to yield 6.5 g of the desired product as a white solid. The filtrate was concentrated under reduced pressure, and the obtained residue was crystallized in EtOAc to afford additional 1.6 g of the title compound (8.1 g in total, 39% yield). LC/MS (method A): retention time=3.30 min, (M+H)+=313. 1H NMR (DMSO-d6, 500 MHz): δ 11.62 (s, 1H), 7.65 (d,J=10 Hz, , 2H), 7.51 (d,J=10 Hz, 2H), 7.23-7.38 (m, 5H), 7.04 (s, 1H), 5.11 (s, 2H). at reflux for 14 h the resulting white suspension was filtered The collected solid was washed with EtOAc (20 mL×2) dried in a 50° C. vacuum oven for 16 h

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

実験手順: To a suspension of 3-(4-chlorophenyl)-2,5-furandione (10.24 g, 66.9 mmol) in acetic acid (300 mL) was added benzylhydrazine dihydrochloride in one portion (19.6 g, 100 mmol). The reaction mixture was stirred at reflux for 14 h. Analysis by HPLC/MS indicated the reaction was complete. After cooling to room temperature, the resulting white suspension was filtered. The collected solid was washed with EtOAc (20 mL×2), and dried in a 50° C. vacuum oven for 16 h to yield 6.5 g of the desired product as a white solid. The filtrate was concentrated under reduced pressure, and the obtained residue was crystallized in EtOAc to afford additional 1.6 g of the title compound (8.1 g in total, 39% yield). LC/MS (method A): retention time=3.30 min, (M+H)+=313. 1H NMR (DMSO-d6, 500 MHz): δ 11.62 (s, 1H), 7.65 (d,J=10 Hz, , 2H), 7.51 (d,J=10 Hz, 2H), 7.23-7.38 (m, 5H), 7.04 (s, 1H), 5.11 (s, 2H). at reflux for 14 h the resulting white suspension was filtered The collected solid was washed with EtOAc (20 mL×2) dried in a 50° C. vacuum oven for 16 h

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

実験手順: To a suspension of 3-(4-chlorophenyl)-2,5-furandione (10.24 g, 66.9 mmol) in acetic acid (300 mL) was added benzylhydrazine dihydrochloride in one portion (19.6 g, 100 mmol). The reaction mixture was stirred at reflux for 14 h. Analysis by HPLC/MS indicated the reaction was complete. After cooling to room temperature, the resulting white suspension was filtered. The collected solid was washed with EtOAc (20 mL×2), and dried in a 50° C. vacuum oven for 16 h to yield 6.5 g of the desired product as a white solid. The filtrate was concentrated under reduced pressure, and the obtained residue was crystallized in EtOAc to afford additional 1.6 g of the title compound (8.1 g in total, 39% yield). LC/MS (method A): retention time=3.30 min, (M+H)+=313. 1H NMR (DMSO-d6, 500 MHz): δ 11.62 (s, 1H), 7.65 (d,J=10 Hz, , 2H), 7.51 (d,J=10 Hz, 2H), 7.23-7.38 (m, 5H), 7.04 (s, 1H), 5.11 (s, 2H). at reflux for 14 h the resulting white suspension was filtered The collected solid was washed with EtOAc (20 mL×2) dried in a 50° C. vacuum oven for 16 h

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

実験手順: To a suspension of 3-(4-chlorophenyl)-2,5-furandione (10.24 g, 66.9 mmol) in acetic acid (300 mL) was added benzylhydrazine dihydrochloride in one portion (19.6 g, 100 mmol). The reaction mixture was stirred at reflux for 14 h. Analysis by HPLC/MS indicated the reaction was complete. After cooling to room temperature, the resulting white suspension was filtered. The collected solid was washed with EtOAc (20 mL×2), and dried in a 50° C. vacuum oven for 16 h to yield 6.5 g of the desired product as a white solid. The filtrate was concentrated under reduced pressure, and the obtained residue was crystallized in EtOAc to afford additional 1.6 g of the title compound (8.1 g in total, 39% yield). HPLC/MS (method A): retention time=3.29 min, (M+H)+=313.1. 1H NMR (DMSO-d6, 500 MHz): δ 11.62 (s, 1H), 7.65 (d, J=10 Hz, , 2H), 7.51 (d, J=10 Hz, 2H), 7.23-7.38 (m, 5H), 7.04 (s, 1H), 5.11 (s, 2H). at reflux for 14 h the resulting white suspension was filtered The collected solid was washed with EtOAc (20 mL×2) dried in a 50° C. vacuum oven for 16 h

反応条件: temp:11.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: With ice-cooling, 15.0 g (72 mmol) of 3-(4-chlorophenyl)furan-2,5-dione were added to 72 ml of thionyl chloride, and the mixture was admixed dropwise over a period 10 min with 11.5 g (145 mmol) of pyridine, the temperature being maintained at 10-12° C. The mixture was stirred at 10-12° C. for 30 min, heated at 75° C. for 10 min using a preheated heating bath and allowed to cool, and excess thionyl chloride was removed at 60° C. under reduced pressure. The residue was boiled with 200 ml of toluene and filtered, and the residue was again boiled with 100 ml of toluene and filtered whilst still hot. The filtrate was concentrated under reduced pressure and the residue was boiled with 100 ml of petroleum ether, cooled, filtered off, washed once more with petroleum ether and dried under reduced pressure. Yield: 16.2 g, m.p. 110-112° C. With ice-cooling heated at 75° C. for 10 min to cool excess thionyl chloride was removed at 60° C. under reduced pressure filtered filtered whilst still hot The filtrate was concentrated under reduced pressure cooled filtered off washed once more with petroleum ether dried under reduced pressure

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: With stirring, 80 ml of concentrated sulfuric acid were added dropwise to 1.38 g (0.57 mol) potassium 3-(4-chlorophenyl)-3-cyanoacrylate in 1.2 1 of 88% strength formic acid. During the addition, the temperature increased to 50° C. The mixture was refluxed for 3 h and, after cooling; put into 10 l of ice-water and then stirred for 1 h, and the product was filtered off, washed with water and dried under reduced pressure. Yield: 86.0 g of m.p. 144-145° C. During the addition The mixture was refluxed for 3 h after cooling stirred for 1 h the product was filtered off washed with water dried under reduced pressure

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

実験手順: 4-Chloro-1,2-phenylenediamine (285 mg) and 2-(4-chlorophenyl)maleic anhydride (420 mg) were dissolved in dichloromethane (4 ml) with heating. The dark solution was stirred at rt for 1 h. The solvent was removed in vacuo and the residue was dissolved in 1M HCl in acetic acid (4 ml). The solution was heated to reflux for 1 h, treated with charcoal, and filtered. From the filtrate the solvent was removed and the residue crystallised from acetone/ethyl acetate to give 3-(5-chloro-2-benzimidazolyl)-2-(4-chlorophenyl)propanoic acid HCl (130 mg) as light orange solid. with heating The solvent was removed in vacuo the residue was dissolved in 1M HCl in acetic acid (4 ml) The solution was heated to reflux for 1 h treated with charcoal filtered From the filtrate the solvent was removed the residue crystallised from acetone/ethyl acetate

反応条件: temp:11.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: With ice-cooling, 15.0 g (72 mmol) of 3-(4-chlorophenyl)furan-2,5-dione were added to 72 ml of thionyl chloride, and the mixture was admixed dropwise over a period 10 min with 11.5 g (145 mmol) of pyridine, the temperature being maintained at 10-12° C. The mixture was stirred at 10-12° C. for 30 min, heated at 75° C. for 10 min using a preheated heating bath and allowed to cool, and excess thionyl chloride was removed at 60° C. under reduced pressure. The residue was boiled with 200 ml of toluene and filtered, and the residue was again boiled with 100 ml of toluene and filtered whilst still hot. The filtrate was concentrated under reduced pressure and the residue was boiled with 100 ml of petroleum ether, cooled, filtered off, washed once more with petroleum ether and dried under reduced pressure. Yield: 16.2 g, m.p. 110-112° C. With ice-cooling heated at 75° C. for 10 min to cool excess thionyl chloride was removed at 60° C. under reduced pressure filtered filtered whilst still hot The filtrate was concentrated under reduced pressure cooled filtered off washed once more with petroleum ether dried under reduced pressure