cyclobutanecarboxamide

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

実験手順: To a solution of 7-bromo-1H-pyrrolo[2,3-c]pyridine (500 mg, 2.53 mmol) in toluene were added tris (dibenzylidene acetone) dipalladium (116.20 mg, 0.126 mmol), Xantphos (32.98 mg, 0.057 mmol), cesium carbonate (896 mg, 2.75 mmol), and cyclobutanecarboxamide (251 mg, 2.96 mmol, Intermediate 4). The resulting reaction mixture was heated to 120° C. and stirred for 8 hours. After cooling to room temperature a saturated aqueous sodium bicarbonate solution (20 mL) was added to the reaction mixture and extracted with ethyl acetate (3×50 mL). The combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel (100-200) column chromatography to afford N-(1H-pyrrolo[2,3-c]pyridin-7-yl)cyclopropane carboxamide (200 mg, 36% yield). The resulting reaction mixture was added to the reaction mixture extracted with ethyl acetate (3×50 mL) The combined organic layer was dried over anhydrous sodium sulfate filtered concentrated The crude product was purified by silica gel (100-200) column chromatography

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

実験手順: (Aminomethyl)cyclobutane was prepared by lithium aluminum hydride reduction of cyclobutanecarboxamide according to the procedure of Shatkina, T. N.: Reutov, O. A., Dokl. Akad. Nauk. SSSR. (1975) 219:1148 [Chem. Abs. 82: 139453m]. Cyclobutanecarboxamide was prepared as follows: a solution of commercially available cyclobutanecarboxylic acid chloride (10 g) in ethyl ether (500 ml) was stirred at 0° while ammonia gas was introduced, resulting in a white precipitate. This material was collected by filtration and redissolved in 50 ml of ethanol/water (4:1, v/v). This solution was applied to a column containing 75 grams of AG 1-X8 ion exchange resin (hydroxide ion form) (obtained from Bio-Rad Company), and elution was continued with ethanol (1 liter). Evaporation of the eluate provided a quantitative yield (8.36 g) of cyclobutanecarboxamide. was introduced resulting in a white precipitate This material was collected by filtration redissolved in 50 ml of ethanol/water (4:1 containing

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

実験手順: To a solution of 7-bromo-1H-pyrrolo[2,3-c]pyridine (500 mg, 2.53 mmol) in toluene were added tris (dibenzylidene acetone)dipalladium (116.20 mg, 0.126 mmol), Xantphos (32.98 mg, 0.057 mmol), cesium carbonate (896 mg, 2.75 mmol), and cyclobutanecarboxamide (251 mg, 2.96 mmol, Intermediate 4). The resulting reaction mixture was heated to 120° C. and stirred for 8 hours. After cooling to room temperature a saturated aqueous sodium bicarbonate solution (20 mL) was added to the reaction mixture and extracted with ethyl acetate (3×50 mL). The combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel (100-200) column chromatography to afford N-(1H-pyrrolo[2,3-c]pyridin-7-yl)cyclopropane carboxamide (200 mg, 36% yield). The resulting reaction mixture was added to the reaction mixture extracted with ethyl acetate (3×50 mL) The combined organic layer was dried over anhydrous sodium sulfate filtered concentrated The crude product was purified by silica gel (100-200) column chromatography

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

実験手順: To a solution of 7-bromo-1H-pyrrolo[2,3-c]pyridine (500 mg, 2.53 mmol) in toluene were added tris (dibenzylidene acetone) dipalladium (116.20 mg, 0.126 mmol), Xantphos (32.98 mg, 0.057 mmol), cesium carbonate (896 mg, 2.75 mmol), and cyclobutanecarboxamide (251 mg, 2.96 mmol, Intermediate 4). The resulting reaction mixture was heated to 120° C. and stirred for 8 hours. After cooling to room temperature a saturated aqueous sodium bicarbonate solution (20 mL) was added to the reaction mixture and extracted with ethyl acetate (3×50 mL). The combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel (100-200) column chromatography to afford N-(1H-pyrrolo[2,3-c]pyridin-7-yl)cyclopropane carboxamide (200 mg, 36% yield). The resulting reaction mixture was added to the reaction mixture extracted with ethyl acetate (3×50 mL) The combined organic layer was dried over anhydrous sodium sulfate filtered concentrated The crude product was purified by silica gel (100-200) column chromatography

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

実験手順: (Aminomethyl)cyclobutane was prepared by lithium aluminum hydride reduction of cyclobutanecarboxamide according to the procedure of Shatkina, T. N.: Reutov, O. A., Dokl. Akad. Nauk. SSSR. (1975) 219:1148 [Chem. Abs. 82: 139453m]. Cyclobutanecarboxamide was prepared as follows: a solution of commercially available cyclobutanecarboxylic acid chloride (10 g) in ethyl ether (500 ml) was stirred at 0° while ammonia gas was introduced, resulting in a white precipitate. This material was collected by filtration and redissolved in 50 ml of ethanol/water (4:1, v/v). This solution was applied to a column containing 75 grams of AG 1-X8 ion exchange resin (hydroxide ion form) (obtained from Bio-Rad Company), and elution was continued with ethanol (1 liter). Evaporation of the eluate provided a quantitative yield (8.36 g) of cyclobutanecarboxamide. was introduced resulting in a white precipitate This material was collected by filtration redissolved in 50 ml of ethanol/water (4:1 containing