氮卓斯汀杂质16

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

实验步骤: 2.00 g (13.0 mmol) of 4-(methylamino)butanoic acid hydrochloride was dissolved in 40 mL of ethanol and 69 μL (1.30 mmol) of concentrated sulfuric acid was added thereto, followed by stirring of the mixture at 90° C. for 1 hour. The solvent was distilled off under reduced pressure, followed by azeotropy with toluene. 3.02 g of the obtained residue was used for the subsequent reaction as such. The solvent was distilled off under reduced pressure 3.02 g of the obtained residue was used for the subsequent reaction as such

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

实验步骤: In 10 mL of dichloromethane, were dissolved 490 mg of 3-(2,6-dichlorophenyl)-4-hydroxy-1,2,5-thiadiazole, and 210 mg of bis(trichloromethyl) carbonate. Thereto, 170 mg of pyridine was added. The mixture was stirred at room temperature for 12 hours. Thereto, 340 mg of 4-(methylamino)butyric acid hydrochloride, and 570 mg of N,N-diisopropylethylamine were added. The mixture was stirred at room temperature for 12 hours. The reaction mixture was poured into water, and was extracted with dichloromethane. The dichloromethane layer was washed with dilute hydrochloric acid, and water successively, dried over anhydrous magnesium sulfate, and concentrated. The concentrate was purified by silica gel column chromatography to obtain 510 mg of N-(3-carboxypropyl)-N-methyl [3-(2,6-dichlorophenyl)-1,2,5-thiadiazol-4-yl] carbamate. The mixture was stirred at room temperature for 12 hours was extracted with dichloromethane The dichloromethane layer was washed with dilute hydrochloric acid, and water successively dried over anhydrous magnesium sulfate concentrated The concentrate was purified by silica gel column chromatography

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

实验步骤: In 10 mL of dichloromethane, were dissolved 490 mg of 3-(2,6-dichlorophenyl)-4-hydroxy-1,2,5-thiadiazole, and 210 mg of bis(trichloromethyl) carbonate. Thereto, 170 mg of pyridine was added. The mixture was stirred at room temperature for 12 hours. Thereto, 340 mg of 4-(methylamino)butyric acid hydrochloride, and 570 mg of N,N-diisopropylethylamine were added. The mixture was stirred at room temperature for 12 hours. The reaction mixture was poured into water, and was extracted with dichloromethane. The dichloromethane layer was washed with dilute hydrochloric acid, and water successively, dried over anhydrous magnesium sulfate, and concentrated. The concentrate was purified by silica gel column chromatography to obtain 510 mg of N-(3-carboxypropyl)-N-methyl [3-(2,6-dichlorophenyl)-1,2,5-thiadiazol-4-yl] carbamate. The mixture was stirred at room temperature for 12 hours was extracted with dichloromethane The dichloromethane layer was washed with dilute hydrochloric acid, and water successively dried over anhydrous magnesium sulfate concentrated The concentrate was purified by silica gel column chromatography

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

实验步骤: 4-(Methylamino)butyric acid hydrochloride (5 g, 32.5 mmol), and potassium carbonate (18 g, 130 mmol) were suspended in water (50 ml) and dioxane (25 ml) then cooled to 0° C. Methyl chloroformate (13 ml, 168 mmol) was added over 1 minute, then the mixture was stirred and allowed to warm slowly to room temperature for 16 hours. Conc. HCl (20 ml) was added then the mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, evaporated and dried in vacuo to give 4-[(methoxycarbonyl)(methyl)amino]butyric acid as a thick clear oil (9.7 g). extracted with ethyl acetate The organic layer was dried over magnesium sulfate evaporated dried in vacuo

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

实验步骤: 4-(Methylamino)butyric acid hydrochloride (5 g, 32.5 mmol), and potassium carbonate (18 g, 130 mmol) were suspended in water (50 ml) and dioxane (25 ml) then cooled to 0° C. Methyl chloroformate (13 ml, 168 mmol) was added over 1 minute, then the mixture was stirred and allowed to warm slowly to room temperature for 16 hours. Conc. HCl (20 ml) was added then the mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, evaporated and dried in vacuo to give 4-[(methoxycarbonyl)(methyl)amino]butyric acid as a thick clear oil (9.7 g). extracted with ethyl acetate The organic layer was dried over magnesium sulfate evaporated dried in vacuo

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

实验步骤: 4-(Methylamino)butanoic acid hydrochloride (22.1 g, 144 mmol) was dissolved in methanol (560 mL), thionyl chloride (42 mL) was added under ice cooling, and then the mixture was stirred at room temperature for 24 hours. After the reaction was completed, the solvent was evaporated under reduced pressure, and the resulting white solid was washed with a mixed solvent of dichloromethane (30 mL) and hexane (300 mL) to give the title compound (21.2 g; yield, 88%) as a white solid. the solvent was evaporated under reduced pressure the resulting white solid was washed with a mixed solvent of dichloromethane (30 mL) and hexane (300 mL)

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

实验步骤: To a solution of KOH (16.5 g, 294 mmol) in H2O (75 ml) was added 4-(methylamino)butyric acid hydrochloride (10, 15.1 g, 98.1 mmol) and the reaction mixture was cooled with an icebath. A solution of 3-(trifluoromethyl)benzenesulfonyl chloride (9, 12.0 g, 49.1 mmol) in THF (75 ml) was dropwise added to the reaction mixture and stirring was continued at room temperature overnight. Aqueous 6 M HCl (75 ml) was added to the reaction mixture while cooling with an icebath, after which CH2Cl2 was added. The organic layer was separated, washed with brine, dried (Na2SO4), concentrated and co-evaporated with a minimal amount of Et2O. Crystallization of the residue out of EtOAc/heptane resulted in AC-08 (11.32 g, 71%). the reaction mixture was cooled with an icebath while cooling with an icebath The organic layer was separated washed with brine dried (Na2SO4) concentrated and co-evaporated with a minimal amount of Et2O Crystallization of the residue out of EtOAc/heptane resulted in AC-08 (11.32 g, 71%)

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

实验步骤: To a solution of KOH (16.5 g, 294 mmol) in H2O (75 ml) was added 4-(methylamino)butyric acid hydrochloride (10, 15.1 g, 98.1 mmol) and the reaction mixture was cooled with an icebath. A solution of 3-(trifluoromethyl)benzenesulfonyl chloride (9, 12.0 g, 49.1 mmol) in THF (75 ml) was dropwise added to the reaction mixture and stirring was continued at room temperature overnight. Aqueous 6 M HCl (75 ml) was added to the reaction mixture while cooling with an icebath, after which CH2Cl2 was added. The organic layer was separated, washed with brine, dried (Na2SO4), concentrated and co-evaporated with a minimal amount of Et2O. Crystallization of the residue out of EtOAc/heptane resulted in AC-08 (11.32 g, 71%). the reaction mixture was cooled with an icebath while cooling with an icebath The organic layer was separated washed with brine dried (Na2SO4) concentrated and co-evaporated with a minimal amount of Et2O Crystallization of the residue out of EtOAc/heptane resulted in AC-08 (11.32 g, 71%)

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

实验步骤: A stirred solution of 7-ethyl-2-isopropyl-2-methyl-5H-imidazo[1′,2′:1,2]pyrrolo[3,4-b]pyridine-3(2H),5-dione (5.47 g, 20.19 mmol) in anhydrous N,N-dimethylformamide is treated successively with 4-(methylamino)butyric acid hydrochloride (3.29 g, 21.2 mmol) and triethylamine (4.29 g, 42.39 mmol). The resulting mixture is stirred at room temperature under nitrogen for 2.5 hours. After this period, the reaction mixture is diluted with water, acidified with concentrated hydrochloric acid and extracted with ether. The organic extract is dried over magnesium sulfate, vacuum filtered through diatomaceous earth and concentrated in vacuo to give the title product as a white solid, mp 42-49° C. (dec.). After this period extracted with ether The organic extract is dried over magnesium sulfate, vacuum filtered through diatomaceous earth concentrated in vacuo

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 4-(methylamino) butyric acid HCl was dissolved in methanol and thionyl chloride in catalytic amount was added drop by drop. The reaction mixture was stirred at 0° C. for 30 min. Thereafter, the solvent was reduced in vacu, yielding a white solid. yielding a white solid

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

实验步骤: A stirred solution of 7-ethyl-2-isopropyl-2-methyl-5H-imidazo[1',2':1,2]pyrrolo[3,4-b]pyridine-3(2H),5-dione (5.47 g, 20.19 mmol) in anhydrous N,N-dimethylformamide is treated successively with 4-(methylamino)butyric acid hydrochloride (3.29 g, 21.2 mmol) and triethylamine (4.29 g, 42.39 mmol). The resulting mixture is stirred at room temperature under nitrogen for 2.5 hours. After this period, the reaction mixture is diluted with water, acidified with concentrated hydrochloric acid and extracted with ether. The organic extract is dried over magnesium sulfate, vacuum filtered through diatomaceous earth and concentrated in vacuo to give the title product as a white solid, mp 42°-49° C. (dec.). After this period extracted with ether The organic extract is dried over magnesium sulfate, vacuum filtered through diatomaceous earth concentrated in vacuo

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

实验步骤: 4-(Methylamino)butanoic acid hydrochloride (10, 15.1 g, 98.1 mmol) was added to a solution of KOH (16.5 g, 294 mmol) in H2O (75 ml) and the reaction mixture was cooled in an ice bath. A solution of 3-(trifluoromethyl)benzenesulfonyl chloride (9, 12.0 g, 49.1 mmol) in THF (75 ml) was added dropwise to the reaction mixture and the mixture was stirred at room temperature overnight. Aqueous 6 M HCl (75 ml) was added, while cooling with an ice bath, and the addition of CH2Cl2 then followed. The organic phase was separated, washed with sat. NaCl solution, dried over Na2SO4 and concentrated and the residue was co-evaporated with a minimal amount of diethyl ether. Recrystallization of the residue from ethyl acetate/heptane gave AC-13 (11.32 g, 71%). the reaction mixture was cooled in an ice bath while cooling with an ice bath The organic phase was separated washed with sat. NaCl solution dried over Na2SO4 concentrated Recrystallization of the residue from ethyl acetate/heptane gave AC-13 (11.32 g, 71%)