3,4-diethyl-1H-pyrrole

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 3,4-diethylpyrrole-2-carboxylate obtained in Step (6) (2.056 g, 10.53 mmol), ethylene glycol (100 ml), and potassium hydroxide (3.5 g) were placed in a light-shielded reaction vessel equipped with a reflux condenser. Then, the inside of the reaction vessel was replaced with nitrogen and the mixture was stirred at 160° C. for 2.5 hours. After that, the reaction solution cooled to room temperature was poured into ice water, and extracted with ethyl acetate, and the extract was washed with an aqueous solution of sodium bicarbonate, water, and a saturated salt solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure, thereby to obtain 3,4-diethylpyrrole. Again, 3,4-diethylpyrrole obtained by this reaction, benzyl-5-acetoxymethyl-4-n-butyl-3-methylpyrrole-2-carboxylate obtained in Step (3) (7.21 g, 21 mmol), acetic acid (10 ml), and ethanol (150 ml) were fed into a light-shielded reaction vessel equipped with a reflux condenser, and was refluxed for 18 hours. After the reflux, the resultant was cooled to room temperature, ethanol (50 ml) was added, and was left standing at 0° C. for 5 hours. The precipitated crystal was filtered out and thoroughly washed with ethanol to yield 2,5-bis(5-benzylcarbonyl-3-n-butyl-4-methyl-2-pyrroylmethyl)-3,4-dimethyl-1H-pyrrole (5.25 g, 72% yield). equipped with a reflux condenser After that, the reaction solution cooled to room temperature extracted with ethyl acetate the extract was washed with an aqueous solution of sodium bicarbonate, water The organic layer was dried over anhydrous sodium sulfate concentrated under reduced pressure

反応条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 3,4-diethylpyrrole-2-carboxylate obtained in Step (6) (2.056 g, 10.53 mmol), ethylene glycol (100 ml), and potassium hydroxide (3.5 g) were placed in a light-shielded reaction vessel equipped with a reflux condenser. Then, the inside of the reaction vessel was replaced with nitrogen and the mixture was stirred at 160° C. for 2.5 hours. After that, the reaction solution cooled to room temperature was poured into ice water, and extracted with ethyl acetate, and the extract was washed with an aqueous solution of sodium bicarbonate, water, and a saturated salt solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure, thereby to obtain 3,4-diethylpyrrole. Again, 3,4-diethylpyrrole obtained by this reaction, benzyl-5-acetoxymethyl-4-n-butyl-3-methylpyrrole-2-carboxylate obtained in Step (3) (7.21 g, 21 mmol), acetic acid (10 ml), and ethanol (150 ml) were fed into a light-shielded reaction vessel equipped with a reflux condenser, and was refluxed for 18 hours. After the reflux, the resultant was cooled to room temperature, ethanol (50 ml) was added, and was left standing at 0° C. for 5 hours. The precipitated crystal was filtered out and thoroughly washed with ethanol to yield 2,5-bis(5-benzylcarbonyl-3-n-butyl-4-methyl-2-pyrroylmethyl)-3,4-dimethyl-1H-pyrrole (5.25 g, 72% yield). equipped with a reflux condenser After that, the reaction solution cooled to room temperature extracted with ethyl acetate the extract was washed with an aqueous solution of sodium bicarbonate, water The organic layer was dried over anhydrous sodium sulfate concentrated under reduced pressure

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: F3, Scheme F. In a 500 mL round bottom flask was placed 250 mL of ethanol from an unopened bottle which is purged with dry nitrogen for ten minutes. 3,4-Diethylpyrrole F2 (1.29 g, 0.01 mol) and 2-acetoxymethyl-5-benzyloxycarbonyl-4-methyl-3 -methoxycarbonylethylpyrrole F1 (7.83 g, 0.02 mol) were added and the mixture heated until all of the pyrroles dissolved. p-Toluenesulfonic acid (65 mg) was added and the reaction temperature maintained at 60° C. The reaction slowly changed color from a clear yellow to a dark red with the product precipitating out of the solution as the reaction progressed. After ten hours the reaction was cooled to room temperature, the volume reduced to one half on a rotary evaporator, and then placed in the freezer for several hours. The product was collected by filtration, washed with a small amount of cold ethanol to afford 4.61 g of an off-white fine powder (61%): 1H NMR (CDCl3, 250 MHz): δ1.14 (6H, t, CH2CH3), 2.23 (6H, s, pyrrole-CH3), 2.31 (4H, t, CH2CH2CO2CH3), 2.50 (4H, q, CH2CH3), 2.64 (4H, t, CH2CH2CO2CH3), 3.60 (10H, br s, CH3CO2 -- and (pyrrole)2 --CH2), 4.44 (4H, br s, C6H5CH2), 6.99-7.02 (4H, m, aromatic), 7.22-7.26 (6H, m, aromatic), 8.72 (1H, s, NH), 10.88 (2H, br s, NH); 13C NMR (CDCl3, 250 MHz): δ10.97, 16.78, 17.71, 19.40, 22.07, 35.09, 51.46, 65.32, 117.37, 119.34, 122.14, 126.58, 126.79, 127.36, 128.19, 133.55, 136.62, 162.35, 173.49; CI MS (M+H)+ 750; HRMS 749.3676 (calc. for C44H51N3O8 : 749.3676). In a 500 mL round bottom flask was placed 250 mL of ethanol from an unopened bottle which is purged with dry nitrogen for ten minutes dissolved The reaction slowly changed color from a clear yellow to a dark red with the product precipitating out of the solution as the reaction After ten hours the reaction was cooled to room temperature the volume reduced to one half on a rotary evaporator placed in the freezer for several hours The product was collected by filtration washed with a small amount of cold ethanol

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

実験手順: 3,4-Diethylpyrrole (Sessler, J. L.; Mozaffari, A.; Johnson, M. R. submitted to Organic Syntheses) (7) (0.62 g, 5.0 mmol), benzyl 5-(acetoxymethyl)-3-ethoxycarbonylmethyl-4-methylpyrrole-2-carboxylate (10) (3.94 g, 10.6 mmol), and p-toluenesulfonic acid monohydrate (152 mg) were dissolved in 50 ml of absolute ethanol and heated at reflux for 4 hours under N2. The resulting suspension was reduced in volume to 30 ml and placed in the freezer for several hours. The product was then collected by filtration, washed with a small amount of cold ethanol, and recrystallized from CH2Cl2 /ethanol to afford compound 11 as a fine, off-white powder (2.13 g, 50%); m.p. 127°-128° C.; 1H NMR (CDCl3) delta 1.28 (6 H, t, J=7.47 HZ, CH2CH3), 1.20 (6 H, t, J=7.07 Hz, OCH2CH3), 2.26 (6 H, s, CH3), 2.48 (4 H, q, J-7.34 HZ, CH2CH3), 3.31 (4 H, s, CH2CO2Et), 3.70 (4 H, s, pyrrole2 --CH2), 4.05 (4 H, q, J=7.09 Hz, OCH2CH3), 4.75 (4 H, br s, CH2Ph), 7.14-7.32 (10 H, m, aromatic), 8.83 (1 H, s, NH), 11.5 (2 H, br s, NH); CIMS, (M+H)+ 778.6; HRMS, 749.3689 (calcd for C44H51N3O8 : 749.3676). heated at reflux for 4 hours under N2 placed in the freezer for several hours The product was then collected by filtration washed with a small amount of cold ethanol recrystallized from CH2Cl2 /ethanol

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

実験手順: condensing two molecular equivalents of benzyl 5-(acetoxymethyl)-4-ethoxycarbonylmethyl-3-methylpyrrole-2-carboxylate with 3,4-diethyl pyrrole under acidic conditions to produce 2,5-bis(5-benzyloxycarbonyl-3-ethoxycarbonylmethyl -4-methylpyrrol-2-ylmethyl)-3,4-diethylpyrrole;

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

実験手順: condensing 3,4-diethylpyrrole with two molecular equivalents of benzyl-5-(acetoxymethyl)-4-ethyl-3-methylpyrrole-2-carboxylate to produce 2,5-bis(5-benzyloxycarbonyl-3-ethyl-4-methylpyrrol-2-ylmethyl)-3,4-diethylpyrrole;

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

実験手順: condensing two molecular equivalents of benzyl 5-(acetoxymethyl)-4-ethoxycarbonylmethyl-3-methylpyrrole-2-carboxylate with 3,4-diethyl pyrrole under acidic conditions to produce 2,5-bis(5-benzyloxycarbonyl-3-ethoxycarbonylmethyl -4-methylpyrrol-2-ylmethyl)-3,4-diethylpyrrole;

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

実験手順: condensing 3,4-diethylpyrrole with two molecular equivalents of benzyl 5-(acetoxymethyl)-4-ethyl-3-methylpyrrole-2-carboxylate to produce 2,5-bis(5-benzyloxycarbonyl-3-ethyl-4-methylpyrrol-2-ylmethyl)-3,4-diethylpyrrole;

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

実験手順: condensing 3,4-diethylpyrrole with two molecular equivalents of benzyl 5-(acetoxymethyl)-4-ethyl-3-methylpyrrole-2-carboxylate to produce 2,5-bis(5-benzyloxycarbonyl-3-ethyl-4-methylpyrrol-2-ylmethyl)-3,4-diethylpyrrole;

反応条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 3,4-diethylpyrrole-2-carboxylate obtained in Step (6) (2.056 g, 10.53 mmol), ethylene glycol (100 ml), and potassium hydroxide (3.5 g) were placed in a light-shielded reaction vessel equipped with a reflux condenser. Then, the inside of the reaction vessel was replaced with nitrogen and the mixture was stirred at 160° C. for 2.5 hours. After that, the reaction solution cooled to room temperature was poured into ice water, and extracted with ethyl acetate, and the extract was washed with an aqueous solution of sodium bicarbonate, water, and a saturated salt solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure, thereby to obtain 3,4-diethylpyrrole. Again, 3,4-diethylpyrrole obtained by this reaction, benzyl-5-acetoxymethyl-4-n-butyl-3-methylpyrrole-2-carboxylate obtained in Step (3) (7.21 g, 21 mmol), acetic acid (10 ml), and ethanol (150 ml) were fed into a light-shielded reaction vessel equipped with a reflux condenser, and was refluxed for 18 hours. After the reflux, the resultant was cooled to room temperature, ethanol (50 ml) was added, and was left standing at 0° C. for 5 hours. The precipitated crystal was filtered out and thoroughly washed with ethanol to yield 2,5-bis(5-benzylcarbonyl-3-n-butyl-4-methyl-2-pyrroylmethyl)-3,4-dimethyl-1H-pyrrole (5.25 g, 72% yield). equipped with a reflux condenser After that, the reaction solution cooled to room temperature extracted with ethyl acetate the extract was washed with an aqueous solution of sodium bicarbonate, water The organic layer was dried over anhydrous sodium sulfate concentrated under reduced pressure