N-(2-氯乙基)邻苯二甲酰亚胺

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of 5,7-dimethyl-1,8-naphthyridin-2(1H)-one (3.5 g., 0.02 mole) in 25 ml. of dry dimethyl formamide under nitrogen atmosphere is added a 57% suspension of sodium hydride in mineral oil (0.84 g., 0.02 mole). This mixture is stirred at room temperature for 1/2 hour. A mixture of N-(2-chloroethyl) phthalimide (4.6 g., 0.022 mole) in 25 ml. of dry dimethylformamide is added to the first suspension. The mixture is stirred at steam bath temperature for 16 hours. On cooling, it is filtered to remove salt and the filtrate evaporated to dryness in vacuo to afford 1-(2-phthalimidoethyl)-5,7-dimethyl-1,8-naphthyridin-2(1H)-one. The mixture is stirred at steam bath temperature for 16 hours On cooling it is filtered to remove salt the filtrate evaporated to dryness in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of 5,7-dimethyl-1,8-naphthyridin-2(1H)-one (3.5 g., 0.02 mole) in 25 ml. of dry dimethyl formamide under nitrogen atmosphere is added a 57% suspension of sodium hydride in mineral oil (0.84 g., 0.02 mole). This mixture is stirred at room temperature for 1/2 hour. A mixture of N-(2-chloroethyl) phthalimide (4.6 g., 0.022 mole) in 25 ml. of dry dimethylformamide is added to the first suspension. The mixture is stirred at steam bath temperature for 16 hours. On cooling, it is filtered to remove salt and the filtrate evaporated to dryness in vacuo to afford 1-(2-phthalimidoethyl)-5,7-dimethyl-1,8-naphthyridin-2(1H)-one. The mixture is stirred at steam bath temperature for 16 hours On cooling it is filtered to remove salt the filtrate evaporated to dryness in vacuo

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-[4-(1-benzofuran-5-yl)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (300 mg, 0.699 mmol) in N,N-dimethylformamide (3 mL) in a 5 mL microwaveable vial was added potassium carbonate (300 mg, 2.1 mmol, 3 eq) and N-(2-chloroethyl)phthalimide (300 mg, 1.43 mmol, 2 eq). The vial was capped and purged with nitrogen gas, and the reaction mixture was stirred for 16 h at 90° C. Analysis by LC/MS displayed the reaction had progressed to 20% completion. The reaction was irradiated in the microwave at 185° C. for 60 min. Analysis by LC/MS displayed the reaction was complete. The reaction mixture was poured into a mixture of dichloromethane and water. The organic layer was separated. The aqueous layer was washed with dichloromethane. The organic extracts were combined and washed 3× with a dilute brine solution. The organic layer was separated, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 30-60% acetonitrile w/0.1% TFA/water w/0.1% TFA). The product fractions were neutralized with the addition of saturated aq sodium bicarbonate, combined, and extracted with dichloromethane. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to afford the intermediate compound (142 mg, 33%). MS(ES)+ m/e 602.0 [M+H]+. The vial was capped purged with nitrogen gas The reaction was irradiated in the microwave at 185° C. for 60 min The reaction mixture was poured into a mixture of dichloromethane and water The organic layer was separated The aqueous layer was washed with dichloromethane washed 3× with a dilute brine solution The organic layer was separated dried over sodium sulfate filtered concentrated in vacuo The crude product was purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 30-60% acetonitrile w/0.1% TFA/water w/0.1% TFA) The product fractions were neutralized with the addition of saturated aq sodium bicarbonate extracted with dichloromethane The organic layer was dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of 50 ml of isopropanol containing N,O-dimethylhydroxylamine hydrochloride (3.90 g, 40.0 mmol) was added dropwise 5.56 ml of triethylamine. The resulting mixture became homogeneous after 5 minutes. Thereto was added 2.45 g (10.0 mmol) of N-(bromoethyl)phthalimide and the mixture was refluxed for 29 hours. This was cooled to room temperature, then poured into 200 ml of a saturated aqueous solution of sodium bicarbonate and extracted with chloroform. The organic layer was separated and was washed with water and dried over magnesium sulfate. Chloroform was distilled off and the residue was purified by column chromatography on silica gel. Development with 30% hexane-chloroform resulted in elution of 1.37 g of N-(2-chloroethyl)-phthalimide and further development with chloroform resulted in 0.964 g (yield: 41%) of white cyrstals of N-[2-(N-methoxy-N-methylamino)ethyl]phthalimide. the mixture was refluxed for 29 hours extracted with chloroform The organic layer was separated was washed with water dried over magnesium sulfate Chloroform was distilled off the residue was purified by column chromatography on silica gel

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of 50 ml of isopropanol containing N,O-dimethylhydroxylamine hydrochloride (3.90 g, 40.0 mmol) was added dropwise 5.56 ml of triethylamine. The resulting mixture became homogeneous after 5 minutes. Thereto was added 2.45 g (10.0 mmol) of N-(bromoethyl)phthalimide and the mixture was refluxed for 29 hours. This was cooled to room temperature, then poured into 200 ml of a saturated aqueous solution of sodium bicarbonate and extracted with chloroform. The organic layer was separated and was washed with water and dried over magnesium sulfate. Chloroform was distilled off and the residue was purified by column chromatography on silica gel. Development with 30% hexane-chloroform resulted in elution of 1.37 g of N-(2-chloroethyl)-phthalimide and further development with chloroform resulted in 0.964 g (yield: 41%) of white cyrstals of N-[2-(N-methoxy-N-methylamino)ethyl]phthalimide. the mixture was refluxed for 29 hours extracted with chloroform The organic layer was separated was washed with water dried over magnesium sulfate Chloroform was distilled off the residue was purified by column chromatography on silica gel

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-[4-(1-benzofuran-5-yl)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (300 mg, 0.699 mmol) in N,N-dimethylformamide (3 mL) in a 5 mL microwaveable vial was added potassium carbonate (300 mg, 2.1 mmol, 3 eq) and N-(2-chloroethyl)phthalimide (300 mg, 1.43 mmol, 2 eq). The vial was capped and purged with nitrogen gas, and the reaction mixture was stirred for 16 h at 90° C. Analysis by LC/MS displayed the reaction had progressed to 20% completion. The reaction was irradiated in the microwave at 185° C. for 60 min. Analysis by LC/MS displayed the reaction was complete. The reaction mixture was poured into a mixture of dichloromethane and water. The organic layer was separated. The aqueous layer was washed with dichloromethane. The organic extracts were combined and washed 3× with a dilute brine solution. The organic layer was separated, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 30-60% acetonitrile w/0.1% TFA/water w/0.1% TFA). The product fractions were neutralized with the addition of saturated aq sodium bicarbonate, combined, and extracted with dichloromethane. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to afford the intermediate compound (142 mg, 33%). MS(ES)+ m/e 602.0 [M+H]+. The vial was capped purged with nitrogen gas The reaction was irradiated in the microwave at 185° C. for 60 min The reaction mixture was poured into a mixture of dichloromethane and water The organic layer was separated The aqueous layer was washed with dichloromethane washed 3× with a dilute brine solution The organic layer was separated dried over sodium sulfate filtered concentrated in vacuo The crude product was purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 30-60% acetonitrile w/0.1% TFA/water w/0.1% TFA) The product fractions were neutralized with the addition of saturated aq sodium bicarbonate extracted with dichloromethane The organic layer was dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-[4-(1-benzofuran-5-yl)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (300 mg, 0.699 mmol) in N,N-dimethylformamide (3 mL) in a 5 mL microwaveable vial was added potassium carbonate (300 mg, 2.1 mmol, 3 eq) and N-(2-chloroethyl)phthalimide (300 mg, 1.43 mmol, 2 eq). The vial was capped and purged with nitrogen gas, and the reaction mixture was stirred for 16 h at 90° C. Analysis by LC/MS displayed the reaction had progressed to 20% completion. The reaction was irradiated in the microwave at 185° C. for 60 min. Analysis by LC/MS displayed the reaction was complete. The reaction mixture was poured into a mixture of dichloromethane and water. The organic layer was separated. The aqueous layer was washed with dichloromethane. The organic extracts were combined and washed 3× with a dilute brine solution. The organic layer was separated, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 30-60% acetonitrile w/0.1% TFA/water w/0.1% TFA). The product fractions were neutralized with the addition of saturated aq sodium bicarbonate, combined, and extracted with dichloromethane. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to afford the intermediate compound (142 mg, 33%). MS(ES)+ m/e 602.0 [M+H]+. The vial was capped purged with nitrogen gas The reaction was irradiated in the microwave at 185° C. for 60 min The reaction mixture was poured into a mixture of dichloromethane and water The organic layer was separated The aqueous layer was washed with dichloromethane washed 3× with a dilute brine solution The organic layer was separated dried over sodium sulfate filtered concentrated in vacuo The crude product was purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 30-60% acetonitrile w/0.1% TFA/water w/0.1% TFA) The product fractions were neutralized with the addition of saturated aq sodium bicarbonate extracted with dichloromethane The organic layer was dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of 5,7-dimethyl-1,8-naphthyridin-2(1H)-one (3.5 g., 0.02 mole) in 25 ml. of dry dimethyl formamide under nitrogen atmosphere is added a 57% suspension of sodium hydride in mineral oil (0.84 g., 0.02 mole). This mixture is stirred at room temperature for 1/2 hour. A mixture of N-(2-chloroethyl) phthalimide (4.6 g., 0.022 mole) in 25 ml. of dry dimethylformamide is added to the first suspension. The mixture is stirred at steam bath temperature for 16 hours. On cooling, it is filtered to remove salt and the filtrate evaporated to dryness in vacuo to afford 1-(2-phthalimidoethyl)-5,7-dimethyl-1,8-naphthyridin-2(1H)-one. The mixture is stirred at steam bath temperature for 16 hours On cooling it is filtered to remove salt the filtrate evaporated to dryness in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of 5,7-dimethyl-1,8-naphthyridin-2(1H)-one (3.5 g., 0.02 mole) in 25 ml. of dry dimethyl formamide under nitrogen atmosphere is added a 57% suspension of sodium hydride in mineral oil (0.84 g., 0.02 mole). This mixture is stirred at room temperature for 1/2 hour. A mixture of N-(2-chloroethyl) phthalimide (4.6 g., 0.022 mole) in 25 ml. of dry dimethylformamide is added to the first suspension. The mixture is stirred at steam bath temperature for 16 hours. On cooling, it is filtered to remove salt and the filtrate evaporated to dryness in vacuo to afford 1-(2-phthalimidoethyl)-5,7-dimethyl-1,8-naphthyridin-2(1H)-one. The mixture is stirred at steam bath temperature for 16 hours On cooling it is filtered to remove salt the filtrate evaporated to dryness in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of 50 ml of isopropanol containing N,O-dimethylhydroxylamine hydrochloride (3.90 g, 40.0 mmol) was added dropwise 5.56 ml of triethylamine. The resulting mixture became homogeneous after 5 minutes. Thereto was added 2.45 g (10.0 mmol) of N-(bromoethyl)phthalimide and the mixture was refluxed for 29 hours. This was cooled to room temperature, then poured into 200 ml of a saturated aqueous solution of sodium bicarbonate and extracted with chloroform. The organic layer was separated and was washed with water and dried over magnesium sulfate. Chloroform was distilled off and the residue was purified by column chromatography on silica gel. Development with 30% hexane-chloroform resulted in elution of 1.37 g of N-(2-chloroethyl)-phthalimide and further development with chloroform resulted in 0.964 g (yield: 41%) of white cyrstals of N-[2-(N-methoxy-N-methylamino)ethyl]phthalimide. the mixture was refluxed for 29 hours extracted with chloroform The organic layer was separated was washed with water dried over magnesium sulfate Chloroform was distilled off the residue was purified by column chromatography on silica gel