4-phenyl-1H-pyrrole-3-carbonitrile

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 5.0 g (39 mmol) of cinnamonitrile and 7.6 g (39 mmol) of (p-tolylsulfonyl)methyl isocyanide in 35 mL of DMSO and 65 mL of ether is added over a 20 minute period a suspension of 1.86 g of a 60% oil suspension of sodium hydride (1.11 g; 46 mmol) in 80 mL of ether. The reaction mixture is maintained under nitrogen for an hour and then diluted with ether and water. The ether layer is separated, dried over magnesium sulfate, and concentrated in vacuo. The resulting oil is chromatographed on silica gel using 1:1 chloroform ethyl acetate to give 2.5 g of cream-colored solids. Recrystallization from etherhexane affords 1.15 g, m.p. 123°-125° C.; NMR M86-1077. is added over a 20 minute period The reaction mixture is maintained under nitrogen for an hour The ether layer is separated dried over magnesium sulfate concentrated in vacuo The resulting oil is chromatographed on silica gel using 1:1 chloroform ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 5.0 g (39 mmol) of cinnamonitrile and 7.6 g (39 mmol) of (p-tolylsulfonyl)methyl isocyanide in 35 mL of DMSO and 65 mL of ether is added over a 20 minute period a suspension of 1.86 g of a 60% oil suspension of sodium hydride (1.11 g; 46 mmol) in 80 mL of ether. The reaction mixture is maintained under nitrogen for an hour and then diluted with ether and water. The ether layer is separated, dried over magnesium sulfate, and concentrated in vacuo. The resulting oil is chromatographed on silica gel using 1:1 chloroform ethyl acetate to give 2.5 g of cream-colored solids. Recrystallization from ether-hexane affords 1.15 g, m.p. 123°-125° C.; NMR M86-1077. is added over a 20 minute period The reaction mixture is maintained under nitrogen for an hour The ether layer is separated dried over magnesium sulfate concentrated in vacuo The resulting oil is chromatographed on silica gel using 1:1 chloroform ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4 g of 3-cyano-4-phenylpyrrole (Compound No. 8) was added to 20 ml of acetic anhydride and heated for 4 hours in oil-bath of 140°-150° C. After cooling, the resulting reaction mixture was poured into about ten-times volume of cold water to decompose excess acetic anhydride. The resulting precipitate was filtrated, washed with water and dried to obtain 4.5 g of crystal. The crystal was recrystallized from methyl alcohol to obtain 3 g of the desired product. heated for 4 hours in oil-bath of 140°-150° C After cooling the resulting reaction mixture The resulting precipitate was filtrated washed with water dried

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 9.50 g (56.5 mmol) of 4-phenyl-1H-pyrrole-3-carbonitrile (CAS 40167-37-1) in 300 ml of acetonitrile are added portionwise 24.0 g (67.8 mmol) of 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (SelectFluor—CAS 140681-55-6), with a certain amount of exothermicity being observed. The mixture is stirred for 18 hours at 60° C. After cooling, the reaction medium is concentrated under reduced pressure and the residue is then taken up in 500 ml of ethyl acetate. The solution is washed twice with 250 ml of water and then with saturated aqueous sodium chloride solution. The organic phase is dried over sodium sulfate and the solvent is evaporated off under reduced pressure to give a brown oil, which is chromatographed on a column of silica gel, eluting with a mixture of 15% ethyl acetate in cyclohexane, to give 3.75 g of 5-fluoro-4-phenyl-1H-pyrrole-3-carbonitrile in the form of a red oil after drying, which product is used as obtained for the rest of the synthesis. After cooling the reaction medium is concentrated under reduced pressure The solution is washed twice with 250 ml of water The organic phase is dried over sodium sulfate the solvent is evaporated off under reduced pressure to give a brown oil, which is chromatographed on a column of silica gel eluting with a mixture of 15% ethyl acetate in cyclohexane

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 9.50 g (56.5 mmol) of 4-phenyl-1H-pyrrole-3-carbonitrile (CAS 40167-37-1) in 300 ml of acetonitrile are added portionwise 24.0 g (67.8 mmol) of 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (SelectFluor—CAS 140681-55-6), with a certain amount of exothermicity being observed. The mixture is stirred for 18 hours at 60° C. After cooling, the reaction medium is concentrated under reduced pressure and the residue is then taken up in 500 ml of ethyl acetate. The solution is washed twice with 250 ml of water and then with saturated aqueous sodium chloride solution. The organic phase is dried over sodium sulfate and the solvent is evaporated off under reduced pressure to give a brown oil, which is chromatographed on a column of silica gel, eluting with a mixture of 15% ethyl acetate in cyclohexane, to give 3.75 g of 5-fluoro-4-phenyl-1H-pyrrole-3-carbonitrile in the form of a red oil after drying, which product is used as obtained for the rest of the synthesis. After cooling the reaction medium is concentrated under reduced pressure The solution is washed twice with 250 ml of water The organic phase is dried over sodium sulfate the solvent is evaporated off under reduced pressure to give a brown oil, which is chromatographed on a column of silica gel eluting with a mixture of 15% ethyl acetate in cyclohexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 44.3 g (263 mmol) of 4-phenyl-1H-pyrrole-3-carbonitrile (CAS 40167-37-1) in 600 ml of tetrahydrofuran are added portionwise 35.8 g (268 mmol) of N-chlorosuccinimide (CAS 128-09-6) and the mixture is then stirred for 48 hours at reflux. After cooling, the reaction medium is concentrated under reduced pressure and the residue is then taken up in water. The reaction product is extracted with ethyl acetate, the organic phase is dried over sodium sulfate and the solvent is evaporated off under reduced pressure to give a brown solid, which is triturated in diisopropyl ether and then isolated by filtration. The filtrate is concentrated under reduced pressure and the solid residue obtained is triturated in diisopropyl ether and then isolated by filtration. The two batches of solid are combined to give 51.7 g of 5-chloro-4-phenyl-1H-pyrrole-3-carbonitrile in the form of a beige-coloured powder after drying. at reflux After cooling the reaction medium is concentrated under reduced pressure The reaction product is extracted with ethyl acetate the organic phase is dried over sodium sulfate the solvent is evaporated off under reduced pressure to give a brown solid, which is triturated in diisopropyl ether isolated by filtration The filtrate is concentrated under reduced pressure the solid residue obtained is triturated in diisopropyl ether isolated by filtration

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 44.3 g (263 mmol) of 4-phenyl-1H-pyrrole-3-carbonitrile (CAS 40167-37-1) in 600 ml of tetrahydrofuran are added portionwise 35.8 g (268 mmol) of N-chlorosuccinimide (CAS 128-09-6) and the mixture is then stirred for 48 hours at reflux. After cooling, the reaction medium is concentrated under reduced pressure and the residue is then taken up in water. The reaction product is extracted with ethyl acetate, the organic phase is dried over sodium sulfate and the solvent is evaporated off under reduced pressure to give a brown solid, which is triturated in diisopropyl ether and then isolated by filtration. The filtrate is concentrated under reduced pressure and the solid residue obtained is triturated in diisopropyl ether and then isolated by filtration. The two batches of solid are combined to give 51.7 g of 5-chloro-4-phenyl-1H-pyrrole-3-carbonitrile in the form of a beige-coloured powder after drying. at reflux After cooling the reaction medium is concentrated under reduced pressure The reaction product is extracted with ethyl acetate the organic phase is dried over sodium sulfate the solvent is evaporated off under reduced pressure to give a brown solid, which is triturated in diisopropyl ether isolated by filtration The filtrate is concentrated under reduced pressure the solid residue obtained is triturated in diisopropyl ether isolated by filtration

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 53.7 g (464 mmol) of potassium tert-butoxide in 500 ml of anhydrous tetrahydrofuran is added dropwise a mixture of 48.5 g (330 mmol) of the mixture of 50.0 g (387 mmol) of cinnamonitrile (CAS 1885-38-7) and 75.6 g (387 mmol) of tosylmethyl isocyanide (CAS 36635-61-7) dissolved in 500 ml of tetrahydrofuran, while maintaining the temperature of the reaction medium at about 25° C. The mixture is then stirred for 1 hour 30 minutes at room temperature and is then poured into saturated sodium chloride solution. The reaction product is then extracted with ethyl acetate, the organic phase is dried over sodium sulfate and the solvent is evaporated off under reduced pressure to give a brown solid, which is dissolved in 350 ml of hot chloroform and purified by chromatography on silica gel, eluting with dichloromethane, to give 44.3 g of 4-phenyl-1H-pyrrole-3-carbonitrile in the form of a beige-coloured powder after triturating in diisopropyl ether, filtering off and drying. is added dropwise The reaction product is then extracted with ethyl acetate the organic phase is dried over sodium sulfate the solvent is evaporated off under reduced pressure to give a brown solid, which purified by chromatography on silica gel eluting with dichloromethane

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-cyano-4-phenylpyrrole (0.20 g) in dimethylsulfoxide (2 mL) was added 5-benzyloxy-2-bromoisonicotinic acid ethyl ester (0.30 g), cesium carbonate (0.30 g), copper iodide (0.010 g) and N,N-dimethyl glycine (0.020 g) at room temperature, and this mixture was stirred at 110° C. for 8 hours. The insoluble material was removed by suction through a Celite pad. This filtrate was poured into water, and this mixture was extracted with ethyl acetate. This organic layer was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate/n-hexane=10/90-60/40) to give the title compound (0.20 g). The insoluble material was removed by suction through a Celite pad This filtrate was poured into water this mixture was extracted with ethyl acetate This organic layer was washed with water and brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by column chromatography on silica gel (eluent: ethyl acetate/n-hexane=10/90-60/40)