3-methyl-1H-pyrrole-2-carbaldehyde

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A reaction mixture of 133.0 mg of oxindole, 130.9 mg of the 3-methylpyrrole-2-carboxaldehyde, and 3 drops of piperidine in 2 mL of ethanol was stirred at 90° C. for 3 h. After cooling, the precipitate was filtered, washed with cold ethanol, and dried to yield 150.9 mg (67%) of the title compound as a yellow solid. After cooling the precipitate was filtered washed with cold ethanol dried

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A reaction mixture of 133.0 mg of oxindole, 130.9 mg of the 3-methylpyrrole-2-carboxaldehyde, and 3 drops of piperidine in 2 mL of ethanol was stirred at 90° C. for 3 h. After cooling, the precipitate was filtered, washed with cold ethanol, and dried to yield 150.9 mg (67%) of the title compound as a yellow solid. After cooling the precipitate was filtered washed with cold ethanol dried

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A reaction mixture of 133.0 mg of oxindole, 130.9 mg of the 3-methylpyrrole-2-carboxaldehyde, and 3 drops of piperidine in 2 mL of ethanol was stirred at 90° C. for 3 h. After cooling, the precipitate was filtered, washed with cold ethanol, and dried to yield 150.9 mg (67%) of the title compound as a yellow solid. After cooling the precipitate was filtered washed with cold ethanol dried

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

Procedure: Methyl-2-pyrrolecarboxaldehyde (5 g), hydroxylamine hydrochloride (9.55 g) and sodium acetate (11.28 g) were dissolved in methanol (100 ml) and the solution was refluxed for 12 hours. Aftre confirming the completion of the reaction using TLC, the resulting mixture was purified by column-chromatography (ethyl acetate/hexane=3/1) to yield the compound (5.01 g, 88%) as a brown solid. the solution was refluxed for 12 hours the resulting mixture was purified by column-chromatography (ethyl acetate/hexane=3/1)

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

Procedure: Methyl-2-pyrrolecarboxaldehyde (5 g), hydroxylamine hydrochloride (9.55 g) and sodium acetate (11.28 g) were dissolved in methanol (100 ml) and the solution was refluxed for 12 hours. Aftre confirming the completion of the reaction using TLC, the resulting mixture was purified by column-chromatography (ethyl acetate/hexane=3/1) to yield the compound (5.01 g, 88%) as a brown solid. the solution was refluxed for 12 hours the resulting mixture was purified by column-chromatography (ethyl acetate/hexane=3/1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following a general procedure,50 a stirred solution of 3-methyl-pyrrole-2-carboxaldehyde (2, 5.63 g, 51.6 mmol) in THF (52 mL) was cooled to 0° C. NBS (9.19 g, 51.6 mmol; reagent grade, unrecrystallized) was added all at once. The reaction mixture was stirred for 15 min at 0° C. under argon before the solvent was removed on a rotary evaporator. The resulting solid was dried under high vacuum for 2 h. Water (100 mL, room temperature) was added to the flask and the suspension was filtered (Büchner funnel). The filter cake was washed with an additional 100 mL of water. The solid filtered material was recrystallized from water/ethanol as follows. The solid filtered material was transferred to a 250 mL round bottom flask equipped with a reflux condenser. Water/ethanol (150 mL, 5:1) were added and the mixture was refluxed in a hot water bath until all solid material had dissolved. Upon allowing the solution to cool to room temperature the product crystallized. The mixture was cooled to 4° C. for 2 h to promote more crystallization. The mixture was vacuum-filtered and the resulting off-white crystals were dried under high vacuum for 24 h (7.78 g, 80%): mp 140-143° C.; 1H NMR δ 2.32 (s, 3H), 7.08 (d, J=3.3 Hz, 1H), 9.60 (s, 1H), 9.95 (brs, 1H); 13C NMR δ 9.8, 101.7, 126.0, 129.3, 131.7, 177.9; ESI-MS obsd 187.9708, calcd 187.9706 [(M+H)+, M=C6H6BrNO]. was removed on a rotary evaporator The resulting solid was dried under high vacuum for 2 h Water (100 mL, room temperature) was added to the flask the suspension was filtered (Büchner funnel) The filter cake was washed with an additional 100 mL of water The solid filtered material was recrystallized from water/ethanol The solid filtered material was transferred to a 250 mL round bottom flask equipped with a reflux condenser Water/ethanol (150 mL, 5:1) were added the mixture was refluxed in a hot water bath until all solid material had dissolved to cool to room temperature the product crystallized The mixture was cooled to 4° C. for 2 h crystallization The mixture was vacuum-filtered the resulting off-white crystals were dried under high vacuum for 24 h (7.78 g, 80%)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A reaction mixture of 133.0 mg of oxindole, 130.9 mg of the 3-methylpyrrole-2-carboxaldehyde, and 3 drops of piperidine in 2 mL of ethanol was stirred at 90° C. for 3 h. After cooling, the precipitate was filtered, washed with cold ethanol, and dried to yield 150.9 mg (67%) of the title compound as a yellow solid. After cooling the precipitate was filtered washed with cold ethanol dried

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 3.15 ml (41 mmol) of DMF at 0° C. under argon was added dropwise 3.81 ml (41 mmol) of phosphorus oxychloride. The cooling bath was removed and stirring was continued for 15 min. The solution was diluted with 9 ml of 1,2-dichloroethane and again cooled to 0° C. A solution of 3.0 g (37 mmol) of 3-methylpyrrole in 9 ml of 1,2-dichloroethane was added dropwise. The mixture was heated to reflux for 15 min, cooled to 0° C. and a solution of 16.2 g (203 mmol) of sodium acetate in 45 ml of water was added with vigorous stirring. The mixture was heated at reflux for 20 min and allowed to cool to room temperature. The aqueous layer was separated and extracted twice with methylene chloride. The combined organic layers were washed with sat NaHCO3 until pH 7, dried (MgSO4), and the solvent removed to yield a dark oily solid which was purified by flash chromatography (10% EtOAc:hexane) to afford 3.6 g (89%) of a 4:1 mixture of 2-formyl-3-methylpyrrole and 2-formyl-4-methylpyrrole as a pale yellow solid. The cooling bath was removed The solution was diluted with 9 ml of 1,2-dichloroethane The mixture was heated to reflux for 15 min cooled to 0° C. The mixture was heated at reflux for 20 min to cool to room temperature The aqueous layer was separated extracted twice with methylene chloride The combined organic layers were washed with sat NaHCO3 until pH 7 dried (MgSO4) the solvent removed to yield a dark oily solid which was purified by flash chromatography (10% EtOAc:hexane) to afford

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 3.15 ml (41 mmol) of DMF at 0° C. under argon was added dropwise 3.81 ml (41 mmol) of phosphorus oxychloride. The cooling bath was removed and stirring was continued for 15 min. The solution was diluted with 9 ml of 1,2-dichloroethane and again cooled to 0° C. A solution of 3.0 g (37 mmol) of 3-methylpyrrole in 9 ml of 1,2-dichloroethane was added dropwise. The mixture was heated to reflux for 15 min, cooled to 0° C. and a solution of 16.2 g (203 mmol) of sodium acetate in 45 ml of water was added with vigorous stirring. The mixture was heated at reflux for 20 min and allowed to cool to room temperature. The aqueous layer was separated and extracted twice with methylene chloride. The combined organic layers were washed with sat NaHCO3 until pH 7, dried (MgSO4), and the solvent removed to yield a dark oily solid which was purified by flash chromatography (10% EtOAc:hexane) to afford 3.6 g (89%) of a 4:1 mixture of 2-formyl-3-methylpyrrole and 2-formyl-4-methylpyrrole as a pale yellow solid. The cooling bath was removed The solution was diluted with 9 ml of 1,2-dichloroethane The mixture was heated to reflux for 15 min cooled to 0° C. The mixture was heated at reflux for 20 min to cool to room temperature The aqueous layer was separated extracted twice with methylene chloride The combined organic layers were washed with sat NaHCO3 until pH 7 dried (MgSO4) the solvent removed to yield a dark oily solid which was purified by flash chromatography (10% EtOAc:hexane) to afford

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 3.15 ml (41 mmol) of DMF at 0° C. under argon was added dropwise 3.81 ml (41 mmol) of phosphorus oxychloride. The cooling bath was removed and stirring was continued for 15 min. The solution was diluted with 9 ml of 1,2-dichloroethane and again cooled to 0° C. A solution of 3.0 g (37 mmol) of 3-methylpyrrole in 9 ml of 1,2-dichloroethane was added dropwise. The mixture was heated to reflux for 15 min, cooled to 0° C. and a solution of 16.2 g (203 mmol) of sodium acetate in 45 ml of water was added with vigorous stirring. The mixture was heated at reflux for 20 min and allowed to cool to room temperature. The aqueous layer was separated and extracted twice with methylene chloride. The combined organic layers were washed with sat NaHCO3 until pH 7, dried (MgSO4), and the solvent removed to yield a dark oily solid which was purified by flash chromatography (10% EtOAc:hexane) to afford 3.6 g (89%) of a 4:1 mixture of 2-formyl-3-methylpyrrole and 2-formyl-4-methylpyrrole as a pale yellow solid. The cooling bath was removed The solution was diluted with 9 ml of 1,2-dichloroethane The mixture was heated to reflux for 15 min cooled to 0° C. The mixture was heated at reflux for 20 min to cool to room temperature The aqueous layer was separated extracted twice with methylene chloride The combined organic layers were washed with sat NaHCO3 until pH 7 dried (MgSO4) the solvent removed to yield a dark oily solid which was purified by flash chromatography (10% EtOAc:hexane) to afford

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A reaction mixture of 133.0 mg of oxindole, 130.9 mg of the 3-methylpyrrole-2-carboxaldehyde, and 3 drops of piperidine in 2 mL of ethanol was stirred at 90° C. for 3 h. After cooling, the precipitate was filtered, washed with cold ethanol, and dried to yield 150.9 mg (67%) of the title compound as a yellow solid. After cooling the precipitate was filtered washed with cold ethanol dried

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 3.15 ml (41 mmol) of DMF at 0° C. under argon was added dropwise 3.81 ml (41 mmol) of phosphorus oxychloride. The cooling bath was removed and stirring was continued for 15 min. The solution was diluted with 9 ml of 1,2-dichloroethane and again cooled to 0° C. A solution of 3.0 g (37 mmol) of 3-methylpyrrole in 9 ml of 1,2-dichloroethane was added dropwise. The mixture was heated to reflux for 15 min, cooled to 0° C. and a solution of 16.2 g (203 mmol) of sodium acetate in 45 ml of water was added with vigorous stirring. The mixture was heated at reflux for 20 min and allowed to cool to room temperature. The aqueous layer was separated and extracted twice with methylene chloride. The combined organic layers were washed with sat NaHCO3 until pH 7, dried (MgSO4), and the solvent removed to yield a dark oily solid which was purified by flash chromatography (10% EtOAc:hexane) to afford 3.6 g (89%) of a 4:1 mixture of 2-formyl-3-methylpyrrole and 2-formyl-4-methylpyrrole as a pale yellow solid. The cooling bath was removed The solution was diluted with 9 ml of 1,2-dichloroethane The mixture was heated to reflux for 15 min cooled to 0° C. The mixture was heated at reflux for 20 min to cool to room temperature The aqueous layer was separated extracted twice with methylene chloride The combined organic layers were washed with sat NaHCO3 until pH 7 dried (MgSO4) the solvent removed to yield a dark oily solid which was purified by flash chromatography (10% EtOAc:hexane) to afford