tert-butyl 1H-pyrrole-3-carboxylate

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

実験手順: To a solution of 2.62 g of tert-butyl 1H-pyrrole-3-carboxylate and 7.96 g of N-(2-bromoethyl)phthalimide in DMF (100 ml) was added 10.2 g of cesium carbonate at room temperature, followed by stirring for 12 hours. The reaction solution was diluted with water and extracted with ethyl acetate. The extract was washed with saturated brine and then dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography using hexane/chloroform as an eluent solvent, and washed with diethyl ether to obtain 670 mg of tert-butyl 1-[2-(1,3-dioxo-1,3-dihydro-2H-isoindo1-2-yl)ethyl]-1H-pyrrole-3-carboxylate as a colorless solid. extracted with ethyl acetate The extract was washed with saturated brine dried over anhydrous magnesium sulfate The organic layer was concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography washed with diethyl ether

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of 1H-pyrrole-3-carboxylic acid tert-butyl ester (700 mg) described in Reference Example 50, 1,1′-bis(diphenylphosphino)ferrocene (35 mg), palladium acetate (9.4 mg), cesium carbonate (1.64 g) and 5-acetyl-2-bromopyridine (921 mg) in toluene (10 ml) was stirred at 100° C. for 8 hours. After completion of the reaction, the mixture was allowed to cool to room temperature, ice water was added thereto, and extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated in vacuo. The obtained residue was purified with silica gel column chromatography (n-hexane/ethyl acetate) to give 1-(5-acetylpyridin-2-yl)pyrrole-3-carboxylic acid tert-butyl ester (380 mg) as a white solid. After completion of the reaction to cool to room temperature extracted with chloroform The organic layer was dried over anhydrous sodium sulfate the solvent was evaporated in vacuo The obtained residue was purified with silica gel column chromatography (n-hexane/ethyl acetate)

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

実験手順: N,N-dimethylethylenediamine (1.9 ml) was added to 1H-pyrrole-3-carboxylic acid tert-butyl ester (2.0 g) described in Reference Example 50, copper iodide (2.28 g), tripotassium phosphate (12.7 g) and 2-bromo-5-chloropyridine (2.78 g) in 1,4-dioxane (120 ml), and stirred at 120° C. for four hours. Water was added to the reaction solution, extracted with ethyl acetate, dried over anhydrous sodium sulfate and concentrated in vacuo. n-Hexane was added to the resulting residue and the precipitated solid was washed with n-hexane to give 1-(5-chloropyridin-2-yl)pyrrole-3-carboxylic acid tert-butyl ester (3.0 g) as a gray solid. extracted with ethyl acetate dried over anhydrous sodium sulfate concentrated in vacuo n-Hexane was added to the resulting residue the precipitated solid was washed with n-hexane

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

実験手順: Sodium hydride (230 mg) was added to a solution of 1H-pyrrole-3-carboxylic acid tert-butyl ester (804 mg) in N,N-dimethylformamide (9.6 ml) at room temperature and stirred at the same temperature for 0.5 hour. 2-Bromo-5-(difluoromethyl)pyridine (1.0 g) was added and stirred at 60° C. for an hour. After completion of the reaction, the reaction solution was cooled to room temperature, water was added and the precipitated solid was filtered. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate) to give 1-[5-(difluoromethyl)pyridin-2-yl]-1H-pyrrole-3-carboxylic acid tert-butyl ester (1.01 g) as a white solid. stirred at 60° C. for an hour After completion of the reaction the precipitated solid was filtered The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate)

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

実験手順: A solution of tert-butyl acrylate (10.5 g) and toluenesulfonylisocyanate (16 g) in tetrahydrofuran (210 ml) was added dropwise at 70° C. to a suspension of sodium hydride (3.9 g) in tetrahydrofuran (200 ml) over 0.5 hour and stirred at the same temperature for two hours. After completion of the reaction, the solvent was evaporated, water was added to the residue and extracted with ethyl acetate three times. The organic layer was dried over anhydrous magnesium sulfate and concentrated. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate) and recrystallized (n-hexane/ethyl acetate) to give the titled compound (5.27 g) as a white solid. After completion of the reaction the solvent was evaporated water was added to the residue extracted with ethyl acetate three times The organic layer was dried over anhydrous magnesium sulfate concentrated The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate) recrystallized (n-hexane/ethyl acetate)

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 0.145 g (0.867 mmol) tert-butylpyrrole-3-carboxylate is dissolved in 10 ml absolute DMSO, mixed with 0.107 g (0.952 mmol) potassium-tert-butylate and stirred at 110° C. for 15 min. A solution of 0.333 g (0.864 mmol) [1-bromo-3-(4-octylphenoxy)propan-2-yl]acetate in 10 ml absolute DMSO is added drop-wise. Following 30 minutes of heating at 110° C. and subsequent cooling, hydrolysis is carried out in saturated NaCl solution. Four extractions with diethyl ether, combination of the organic phases, concentration to half the volume on the rotary evaporator, three wash steps using saturated NaCl solution, drying on sodium sulfate, filtration and reconcentration on the rotary evaporator leave as a crude product a yellow oil which is purified on silica gel by means of flash column chromatography (flow agent: petroleum ether/ethyl acetate 93:7) and yields the product as a colorless oil. Following 30 minutes of heating at 110° C. subsequent cooling, hydrolysis Four extractions with diethyl ether, combination of the organic phases, concentration to half the volume on the rotary evaporator, three wash steps drying on sodium sulfate, filtration and reconcentration on the rotary evaporator leave as a crude product a yellow oil which is purified on silica gel by means of flash column chromatography (flow agent: petroleum ether/ethyl acetate 93:7)

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

実験手順: 0.50 g (4.50 mmol) pyrrole-3-carboxylic acid is suspended in 15 ml absolute benzene and boiled under reflux. A solution 4.07 g (18.0 mmol) 90% N,N-dimethylformamidedi-tert-butylacetal in 15 ml absolute benzene is added drop-wise within 30 min. Following another heating under reflux for 30 minutes and subsequent cooling, the reaction mixture is diluted with diethyl ether, washed with 5% sodium carbonate solution and saturated NaCl solution. Drying on sodium sulfate, filtration and concentration on the rotary evaporator leave as a crude product a yellow solid which is purified on silica gel by means of column chromatography (flow agent: petroleum ether/ethyl acetate 90:10) and yields the product as a white solid. under reflux under reflux for 30 minutes washed with 5% sodium carbonate solution and saturated NaCl solution Drying on sodium sulfate, filtration and concentration on the rotary evaporator leave as a crude product a yellow solid which is purified on silica gel by means of column chromatography (flow agent: petroleum ether/ethyl acetate 90:10)

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

実験手順: Sodium hydride (60%; 1.02 mg) was added at 0° C. to a solution of 1H-pyrrole-3-carboxylic acid tert-butyl ester (3.57 g) in tetrahydrofuran (71 ml), stirred at room temperature, then p-toluenesulfonic acid chloride (4.47 g) the mixture was stirred all night and all day. Water was added to the reaction solution, extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous sodium sulfate. The organic solution was concentrated in vacuo, dichloromethane (30 ml) and trifluoroacetic acid (15 ml) were added to the resulting residue and stirred at room temperature for four hours. The solvent was evaporated, water was added to the resulting residue and the precipitated solid was washed with water to give 1-[(4-methylphenyl)sulfonyl]-1H-pyrrole-3-carboxylic acid (4.2 g) as a pale yellow solid. extracted with ethyl acetate washed with saturated brine dried over anhydrous sodium sulfate The organic solution was concentrated in vacuo, dichloromethane (30 ml) and trifluoroacetic acid (15 ml) were added to the resulting residue stirred at room temperature for four hours The solvent was evaporated water was added to the resulting residue the precipitated solid was washed with water

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

実験手順: To a solution of 2.62 g of tert-butyl 1H-pyrrole-3-carboxylate and 7.96 g of N-(2-bromoethyl)phthalimide in DMF (100 ml) was added 10.2 g of cesium carbonate at room temperature, followed by stirring for 12 hours. The reaction solution was diluted with water and extracted with ethyl acetate. The extract was washed with saturated brine and then dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography using hexane/chloroform as an eluent solvent, and washed with diethyl ether to obtain 670 mg of tert-butyl 1-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-1H-pyrrole-3-carboxylate as a colorless solid. extracted with ethyl acetate The extract was washed with saturated brine dried over anhydrous magnesium sulfate The organic layer was concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography washed with diethyl ether

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

実験手順: To a solution of 2.62 g of tert-butyl 1H-pyrrole-3-carboxylate and 7.96 g of N-(2-bromoethyl)phthalimide in DMF (100 ml) was added 10.2 g of cesium carbonate at room temperature, followed by stirring for 12 hours. The reaction solution was diluted with water and extracted with ethyl acetate. The extract was washed with saturated brine and then dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography using hexane/chloroform as an eluent solvent, and washed with diethyl ether to obtain 670 mg of tert-butyl 1-[2-(1,3-dioxo-1,3-dihydro-2H-isoindo1-2-yl)ethyl]-1H-pyrrole-3-carboxylate as a colorless solid. extracted with ethyl acetate The extract was washed with saturated brine dried over anhydrous magnesium sulfate The organic layer was concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography washed with diethyl ether