1-(氨基甲基)-环庚醇盐酸盐

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

实验步骤: Acetyl chloride (264 ml) and tetrahydrofuran (191 ml) were charged to a vessel containing 2-propanol (1143 ml) maintaining the temperature at 10° C. to 15° C. 1-(aminomethyl)cycloheptanol (381 g) in tetrahydrofuran (1613 ml) and tetrahydrofuran (381 ml) were charged maintaining the temperature at 10° C. to 15° C. The reaction mixture was stirred for 50 minutes and filtered. The filter cake was washed with premixed tetrahydrofuran/2-propanol [tetrahydrofuran (267 ml), 2-propanol (114 ml)], and tetrahydrofuran (1905 ml). The filter cake was dried at 40° C. for 23 hours to provide the title compound as a colourless solid (464 g). maintaining the temperature at 10° C. to 15° C maintaining the temperature at 10° C. to 15° C filtered The filter cake was washed with premixed tetrahydrofuran/2-propanol [tetrahydrofuran (267 ml), 2-propanol (114 ml)], and tetrahydrofuran (1905 ml) The filter cake was dried at 40° C. for 23 hours

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

实验步骤: A slurry of 5-(3,5-Dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-2-methyl-benzoic acid (5.0 g, 20.2 mmol), 1-aminomethyl-cycloheptanol HCl (5.4 g, 30.3 mmol), EDCl (5.8 g), and DMAP (7.4 g, 60.6 mmol) in DMF (67.3 mL) was stirred at ambient temperature for 14 hours. The reaction was then poured into 1N HCl (50 mL) and diluted with water (15 fold). The aqueous was extracted with CH2Cl2 (3×). The organics were combined, washed with brine, dried over sodium sulfate, and concentrated in vacuo to give a tan solid. The crude was recrystallized from CH2Cl2 to give the title compound as an off-white solid (3.1 g). The aqueous was extracted with CH2Cl2 (3×) washed with brine dried over sodium sulfate concentrated in vacuo to give a tan solid The crude was recrystallized from CH2Cl2

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

实验步骤: A slurry of 5-(3,5-Dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-2-methyl-benzoic acid (5.0 g, 20.2 mmol), 1-aminomethyl-cycloheptanol HCl (5.4 g, 30.3 mmol), EDCI (5.8 g), and DMAP (7.4 g, 60.6 mmol) in DMF (67.3 mL) was stirred at ambient temperature for 14 hours. The reaction was then poured into 1N HCl (50 mL) and diluted with water (15 fold). The aqueous was extracted with CH2Cl2 (3×). The organics were combined, washed with brine, dried over sodium sulfate, and concentrated in vacuo to give a tan solid. The crude was recrystallized from CH2Cl2 to give the title compound as an off-white solid (3.1 g). The aqueous was extracted with CH2Cl2 (3×) washed with brine dried over sodium sulfate concentrated in vacuo to give a tan solid The crude was recrystallized from CH2Cl2

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

实验步骤: A slurry of 5-(3,5-Dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-2-methyl-benzoic acid (5.0 g, 20.2 mmol), 1-aminomethyl-cycloheptanol HCl (5.4 g, 30.3 mmol), EDCI (5.8 g), and DMAP (7.4 g, 60.6 mmol) in DMF (67.3 mL) was stirred at ambient temperature for 14 hours. The reaction was then poured into 1N HCl (50 mL) and diluted with water (15 fold). The aqueous was extracted with CH2Cl2 (3×). The organics were combined, washed with brine, dried over sodium sulfate, and concentrated in vacuo to give a tan solid. The crude was recrystallized from CH2Cl2 to give the title compound as an off-white solid (3.1 g). The aqueous was extracted with CH2Cl2 (3×) washed with brine dried over sodium sulfate concentrated in vacuo to give a tan solid The crude was recrystallized from CH2Cl2

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

实验步骤: To a solution of 2-chloro-5-(2H-[1,2,3]triazol-4-yl)-benzoic acid (0.03 g, 0.136 mmol) in DMF (1.0 mL) was added 1-hydroxybenzotriazole (28 mg, 0.204 mmol), polystyrene supported 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (0.4 g, 0.4 mmol) and 1-aminomethyl-cycloheptanol hydrochloride (0.036 g, 0.204 mmol). The mixture was stirred at room temperature for 10 minutes, then polystyrene supported N,N-dimethylaminopyridine (0.2 g, 0.29 mmol) was added and the mixture was shaken at room temperature for 16 h. MP-carbonate was added (200 mg) and the mixture was shaken at room temperature for 3 h. The mixture was filtered and washed with methanol. the filtrate was concentrated in vacuo and purified by reverse phase chromatography to afford the title compound (22 mg). LCMS (m/z) 349.3 M+1. was added the mixture was shaken at room temperature for 16 h the mixture was shaken at room temperature for 3 h The mixture was filtered washed with methanol the filtrate was concentrated in vacuo purified by reverse phase chromatography

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

实验步骤: To a solution of 2-chloro-5-(5-methyl-1H-pyrazol-3-yl)-benzoic acid (100 mg, 0.422 mmol) in DMF (10 mL) was added 1-hydroxybenzotriazole (85 mg, 0.63 mmol), polystyrene supported 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (1.24 g, 1.27 mmol) and 1-aminomethyl-cycloheptanol hydrochloride (113.4 mg, 0.633 mmol). The mixture was stirred at room temperature for 15 minutes, then polystyrene supported N,N-dimethylaminopyridine (0.64 g, 0.93 mmol) was added and the mixture was stirred at room temperature for 16 h. The mixture was filtered through a glass frit, and the residue was washed thoroughly with methanol. The filtrate was concentrated to dryness in vacuo. The residue was purified by reverse phase chormatography to afford the title compound as a white solid (40 mg). LC/MS (M/z): 362.5 (M+1). was added the mixture was stirred at room temperature for 16 h The mixture was filtered through a glass frit the residue was washed thoroughly with methanol The filtrate was concentrated to dryness in vacuo The residue was purified by reverse phase chormatography

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

实验步骤: Acetyl chloride (264 ml) and tetrahydrofuran (191 ml) were charged to a vessel containing 2-propanol (1143 ml) maintaining the temperature at 10° C. to 15° C. 1-(aminomethyl)cycloheptanol (381 g) in tetrahydrofuran (1613 ml) and tetrahydrofuran (381 ml) were charged maintaining the temperature at 10° C. to 15° C. The reaction mixture was stirred for 50 minutes and filtered. The filter cake was washed with premixed tetrahydrofuran/2-propanol [tetrahydrofuran (267 ml), 2-propanol (114 ml)], and tetrahydrofuran (1905 ml). The filter cake was dried at 40° C. for 23 hours to provide the title compound as a colourless solid (464 g). maintaining the temperature at 10° C. to 15° C maintaining the temperature at 10° C. to 15° C filtered The filter cake was washed with premixed tetrahydrofuran/2-propanol [tetrahydrofuran (267 ml), 2-propanol (114 ml)], and tetrahydrofuran (1905 ml) The filter cake was dried at 40° C. for 23 hours

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

实验步骤: A slurry of 5-(3,5-Dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-2-methyl-benzoic acid (5.0 g, 20.2 mmol), 1-aminomethyl-cycloheptanol HCl (5.4 g, 30.3 mmol), EDCl (5.8 g), and DMAP (7.4 g, 60.6 mmol) in DMF (67.3 mL) was stirred at ambient temperature for 14 hours. The reaction was then poured into 1N HCl (50 mL) and diluted with water (15 fold). The aqueous was extracted with CH2Cl2 (3×). The organics were combined, washed with brine, dried over sodium sulfate, and concentrated in vacuo to give a tan solid. The crude was recrystallized from CH2Cl2 to give the title compound as an off-white solid (3.1 g). The aqueous was extracted with CH2Cl2 (3×) washed with brine dried over sodium sulfate concentrated in vacuo to give a tan solid The crude was recrystallized from CH2Cl2

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

实验步骤: A slurry of 5-(3,5-Dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-2-methyl-benzoic acid (5.0 g, 20.2 mmol), 1-aminomethyl-cycloheptanol HCl (5.4 g, 30.3 mmol), EDCl (5.8 g), and DMAP (7.4 g, 60.6 mmol) in DMF (67.3 mL) was stirred at ambient temperature for 14 hours. The reaction was then poured into 1N HCl (50 mL) and diluted with water (15 fold). The aqueous was extracted with CH2Cl2 (3×). The organics were combined, washed with brine, dried over sodium sulfate, and concentrated in vacuo to give a tan solid. The crude was recrystallized from CH2Cl2 to give the title compound as an off-white solid (3.1 g). The aqueous was extracted with CH2Cl2 (3×) washed with brine dried over sodium sulfate concentrated in vacuo to give a tan solid The crude was recrystallized from CH2Cl2

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

实验步骤: A slurry of 5-(3,5-Dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-2-methyl-benzoic acid (5.0 g, 20.2 mmol), 1-aminomethyl-cycloheptanol HCl (5.4 g, 30.3 mmol), EDCI (5.8 g), and DMAP (7.4 g, 60.6 mmol) in DMF (67.3 mL) was stirred at ambient temperature for 14 hours. The reaction was then poured into 1N HCl (50 mL) and diluted with water (15 fold). The aqueous was extracted with CH2Cl2 (3×). The organics were combined, washed with brine, dried over sodium sulfate, and concentrated in vacuo to give a tan solid. The crude was recrystallized from CH2Cl2 to give the title compound as an off-white solid (3.1 g). The aqueous was extracted with CH2Cl2 (3×) washed with brine dried over sodium sulfate concentrated in vacuo to give a tan solid The crude was recrystallized from CH2Cl2

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

实验步骤: A slurry of 5-(3,5-Dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-2-methyl-benzoic acid (5.0 g, 20.2 mmol), 1-aminomethyl-cycloheptanol HCl (5.4 g, 30.3 mmol), EDCI (5.8 g), and DMAP (7.4 g, 60.6 mmol) in DMF (67.3 mL) was stirred at ambient temperature for 14 hours. The reaction was then poured into 1N HCl (50 mL) and diluted with water (15 fold). The aqueous was extracted with CH2Cl2 (3×). The organics were combined, washed with brine, dried over sodium sulfate, and concentrated in vacuo to give a tan solid. The crude was recrystallized from CH2Cl2 to give the title compound as an off-white solid (3.1 g). The aqueous was extracted with CH2Cl2 (3×) washed with brine dried over sodium sulfate concentrated in vacuo to give a tan solid The crude was recrystallized from CH2Cl2

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

实验步骤: A slurry of 5-(3,5-Dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-2-methyl-benzoic acid (5.0 g, 20.2 mmol), 1-aminomethyl-cycloheptanol HCl (5.4 g, 30.3 mmol), EDCI (5.8 g), and DMAP (7.4 g, 60.6 mmol) in DMF (67.3 mL) was stirred at ambient temperature for 14 hours. The reaction was then poured into 1N HCl (50 mL) and diluted with water (15 fold). The aqueous was extracted with CH2Cl2 (3×). The organics were combined, washed with brine, dried over sodium sulfate, and concentrated in vacuo to give a tan solid. The crude was recrystallized from CH2Cl2 to give the title compound as an off-white solid (3.1 g). The aqueous was extracted with CH2Cl2 (3×) washed with brine dried over sodium sulfate concentrated in vacuo to give a tan solid The crude was recrystallized from CH2Cl2