4-methoxy-1H-indole-3-carbaldehyde

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

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

Procedure: 4-MethoxyIndole-3-carboxaldehyde (5.0 g) and Meldrum's acid (2,2-Dimethyl-[1,3]dioxane-4,6-dione, 4.11 g) were mixed in toluene (200 ml). To this mixture was added 0.6 ml each of piperidine and acetic acid. The reaction mixture was stirred at room temperature for four hours. The precipitate was filtered and washed with toluene to afford 4.25 g of crude 5-(4-methoxy-1H-indol-3-ylmethylene)-2,2-dimethyl-[1,3]dioxane-4,6-dione as an orange solid which was used without further purification. The precipitate was filtered washed with toluene

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

Procedure: 4-MethoxyIndole-3-carboxaldehyde (5.0 g) and Meldrum's acid (2,2-Dimethyl-[1,3]dioxane-4,6-dione, 4.11 g) were mixed in toluene (200 ml). To this mixture was added 0.6 ml each of piperidine and acetic acid. The reaction mixture was stirred at room temperature for four hours. The precipitate was filtered and washed with toluene to afford 4.25 g of crude 5-(4-methoxy-1H-indol-3-ylmethylene)-2,2-dimethyl-[1,3]dioxane-4,6-dione as an orange solid which was used without further purification. The precipitate was filtered washed with toluene

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

Procedure: A solution of dry DMF (0.75 g) in 50 ml dichloroethane was cooled to 0° C. and placed under nitrogen. Oxalyl chloride (1.03 g) dissolved in dichloroethane (5 ml) was added dropwise with stirring. The solution was stirred until no more bubbling was observed (about 15-20 m). 4-Methoxyindole (1.0 g, 6.7 mmole) was added to the solution as a solid and the reaction mixture was stirred at room temperature for four hours. The reaction was quenched by careful addition of 10% sodium carbonate solution. The two phase mixture was stirred at room temperature for 2 hours. The layers were separated and the aqueous layer was extracted with methylene chloride, and the combined organic extracts were dried and evaporated to dryness. The crude residue was passed through a short silica gel column, eluting with 3:7 ethyl acetate:hexane to 1:1 ethyl acetate:hexane to yield 1.13 g (95%) of 4-methoxy-1H-indole-3-carbaldehyde. was added dropwise The solution was stirred until no more bubbling the reaction mixture was stirred at room temperature for four hours The reaction was quenched by careful addition of 10% sodium carbonate solution The two phase mixture was stirred at room temperature for 2 hours The layers were separated the aqueous layer was extracted with methylene chloride the combined organic extracts were dried evaporated to dryness eluting with 3:7 ethyl acetate

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

Procedure: A solution of dry DMF (0.75 g) in 50 ml dichloroethane was cooled to 0° C. and placed under nitrogen. Oxalyl chloride (1.03 g) dissolved in dichloroethane (5 ml) was added dropwise with stirring. The solution was stirred until no more bubbling was observed (about 15-20 m). 4-Methoxyindole (1.0 g, 6.7 mmole) was added to the solution as a solid and the reaction mixture was stirred at room temperature for four hours. The reaction was quenched by careful addition of 10% sodium carbonate solution. The two phase mixture was stirred at room temperature for 2 hours. The layers were separated and the aqueous layer was extracted with methylene chloride, and the combined organic extracts were dried and evaporated to dryness. The crude residue was passed through a short silica gel column, eluting with 3:7 ethyl acetate:hexane to 1:1 ethyl acetate:hexane to yield 1.13 g (95%) of 4-methoxy-1H-indole-3-carbaldehyde. was added dropwise The solution was stirred until no more bubbling the reaction mixture was stirred at room temperature for four hours The reaction was quenched by careful addition of 10% sodium carbonate solution The two phase mixture was stirred at room temperature for 2 hours The layers were separated the aqueous layer was extracted with methylene chloride the combined organic extracts were dried evaporated to dryness eluting with 3:7 ethyl acetate

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

Procedure: 4-MethoxyIndole-3-carboxaldehyde (5.0 g) and Meldrum's acid (2,2-Dimethyl-[1,3]dioxane-4,6-dione, 4.11 g) were mixed in toluene (200 ml). To this mixture was added 0.6 ml each of piperidine and acetic acid. The reaction mixture was stirred at room temperature for four hours. The precipitate was filtered and washed with toluene to afford 4.25 g of crude 5-(4-methoxy-1H-indol-3-ylmethylene)-2,2-dimethyl-[1,3]dioxane-4,6-dione as an orange solid which was used without further purification. The precipitate was filtered washed with toluene

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

Procedure: A solution of dry DMF (0.75 g) in 50 ml dichloroethane was cooled to 0° C. and placed under nitrogen. Oxalyl chloride (1.03 g) dissolved in dichloroethane (5 ml) was added dropwise with stirring. The solution was stirred until no more bubbling was observed (about 15-20 m). 4-Methoxyindole (1.0 g, 6.7 mmole) was added to the solution as a solid and the reaction mixture was stirred at room temperature for four hours. The reaction was quenched by careful addition of 10% sodium carbonate solution. The two phase mixture was stirred at room temperature for 2 hours. The layers were separated and the aqueous layer was extracted with methylene chloride, and the combined organic extracts were dried and evaporated to dryness. The crude residue was passed through a short silica gel column, eluting with 3:7 ethyl acetate:hexane to 1:1 ethyl acetate:hexane to yield 1.13 g (95%) of 4-methoxy-1H-indole-3-carbaldehyde. was added dropwise The solution was stirred until no more bubbling the reaction mixture was stirred at room temperature for four hours The reaction was quenched by careful addition of 10% sodium carbonate solution The two phase mixture was stirred at room temperature for 2 hours The layers were separated the aqueous layer was extracted with methylene chloride the combined organic extracts were dried evaporated to dryness eluting with 3:7 ethyl acetate

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

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

Procedure: Add phosphorus oxychloride (1.1 eq.) with vigorous stirring to DMF (cooled in an ice bath). After the addition is complete, allow to stir in the ice bath for ˜10 minutes, then add a solution of 4-methoxy-1H-indole (5 g) in anhydrous DMF with vigorous stirring. Allow to stir at 0° C. After 1 hour, warm to room temperature. After 16 hours, carefully add 4 eq. of 2N NaOH with vigorous stirring. Heat to about 80° C. and then cool. Pour the reaction mixture into cold water with vigorous stirring to give a solid. Collect the solid by filtration and dry in a vacuum oven at room temperature to give the title compound. Acidify the filtrate and extract with EtOAc. Combine the organic layers and wash with 50% brine. Collect the organic layer, dry (MgSO4) filter, and remove the solvent to give the title compound as a light purple solid. Total yield of the title compound is 5.44 g: MS (ES+): m/z 175 (M+H)+, 160 (M−CH3)+; (ES−): m/z 174 (M−H)−. After the addition warm to room temperature After 16 hours Heat to about 80° C. cool with vigorous stirring to give a solid Collect the solid by filtration dry in a vacuum oven at room temperature

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

Procedure: Add phosphorus oxychloride (1.1 eq.) with vigorous stirring to DMF (cooled in an ice bath). After the addition is complete, allow to stir in the ice bath for ˜10 minutes, then add a solution of 4-methoxy-1H-indole (5 g) in anhydrous DMF with vigorous stirring. Allow to stir at 0° C. After 1 hour, warm to room temperature. After 16 hours, carefully add 4 eq. of 2N NaOH with vigorous stirring. Heat to about 80° C. and then cool. Pour the reaction mixture into cold water with vigorous stirring to give a solid. Collect the solid by filtration and dry in a vacuum oven at room temperature to give the title compound. Acidify the filtrate and extract with EtOAc. Combine the organic layers and wash with 50% brine. Collect the organic layer, dry (MgSO4) filter, and remove the solvent to give the title compound as a light purple solid. Total yield of the title compound is 5.44 g: MS (ES+): m/z 175 (M+H)+, 160 (M-CH3)+; (ES−): m/z 174 (M−H)−. After the addition warm to room temperature After 16 hours Heat to about 80° C. cool with vigorous stirring to give a solid Collect the solid by filtration dry in a vacuum oven at room temperature

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

Procedure: 4-MethoxyIndole-3-carboxaldehyde (5.0 g) and Meldrum's acid (2,2-Dimethyl-[1,3]dioxane-4,6-dione, 4.11 g) were mixed in toluene (200 ml). To this mixture was added 0.6 ml each of piperidine and acetic acid. The reaction mixture was stirred at room temperature for four hours. The precipitate was filtered and washed with toluene to afford 4.25 g of crude 5-(4-methoxy-1H-indol-3-ylmethylene)-2,2-dimethyl-[1,3]dioxane-4,6-dione as an orange solid which was used without further purification. The precipitate was filtered washed with toluene

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

Procedure: A solution of dry DMF (0.75 g) in 50 ml dichloroethane was cooled to 0° C. and placed under nitrogen. Oxalyl chloride (1.03 g) dissolved in dichloroethane (5 ml) was added dropwise with stirring. The solution was stirred until no more bubbling was observed (about 15-20 m). 4-Methoxyindole (1.0 g, 6.7 mmole) was added to the solution as a solid and the reaction mixture was stirred at room temperature for four hours. The reaction was quenched by careful addition of 10% sodium carbonate solution. The two phase mixture was stirred at room temperature for 2 hours. The layers were separated and the aqueous layer was extracted with methylene chloride, and the combined organic extracts were dried and evaporated to dryness. The crude residue was passed through a short silica gel column, eluting with 3:7 ethyl acetate:hexane to 1:1 ethyl acetate:hexane to yield 1.13 g (95%) of 4-methoxy-1H-indole-3-carbaldehyde. was added dropwise The solution was stirred until no more bubbling the reaction mixture was stirred at room temperature for four hours The reaction was quenched by careful addition of 10% sodium carbonate solution The two phase mixture was stirred at room temperature for 2 hours The layers were separated the aqueous layer was extracted with methylene chloride the combined organic extracts were dried evaporated to dryness eluting with 3:7 ethyl acetate