methyl 6-bromo-1H-indole-3-carboxylate

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:

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

Procedure: To a solution of 6-bromoindole-3-carboxylic acid (960 mg, 4.00 mmol) in methanol (9.5 mL) is added (trimethylsilyl)diazomethane (2.0 M solution in hexanes, ca 9 mL) over two minutes at room temperature. The yellow mixture is concentrated under reduced pressure. The residue is redissolved in methanol and concentrated under reduced pressure. This process is repeated several times to give the title compound as a solid (100%). ES/MS m/e 256.0 (M+2). The yellow mixture is concentrated under reduced pressure The residue is redissolved in methanol concentrated under reduced pressure

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

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

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6-bromo-1H-indole-3-carboxylic acid methyl ester (500 mg, 1.97 mmol), sodium hydride (60% in mineral oil, 748 mg, 31.2 mmol), sodium iodide (295 mg, 1.96 mmol), 2-dimethylaminoethyl chloride hydrochloride (341 mg, 2.37 mmol) and DMF (60 mL) is heated at 100° C. for 8 hours. The reaction mixture is cooled, filtered, and the solids are washed with water and air dried. The solids are dissolved in MeOH (200 mL) and (trimethylsilyl)diazomethane (2.0 M solution in hexanes, 20 mL) is added over several minutes. The reaction mixture is stirred for one hour and concentrated under reduced pressure. The residue is partitioned between water and ethyl acetate. The ethyl acetate layer is separated and dried over MgSO4. The crude product is purified via radial chromatography using 2.5% MeOH/CH2Cl2 to afford the title compound (195 mg, 30%). ES/MS m/e 327.0 (M+2). The reaction mixture is cooled filtered the solids are washed with water and air dried The solids are dissolved in MeOH (200 mL) (trimethylsilyl)diazomethane (2.0 M solution in hexanes, 20 mL) is added over several minutes concentrated under reduced pressure The residue is partitioned between water and ethyl acetate The ethyl acetate layer is separated dried over MgSO4 The crude product is purified via radial chromatography

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6-bromo-1H-indole-3-carboxylic acid methyl ester (500 mg, 1.97 mmol), sodium hydride (60% in mineral oil, 748 mg, 31.2 mmol), sodium iodide (295 mg, 1.96 mmol), 2-dimethylaminoethyl chloride hydrochloride (341 mg, 2.37 mmol) and DMF (60 mL) is heated at 100° C. for 8 hours. The reaction mixture is cooled, filtered, and the solids are washed with water and air dried. The solids are dissolved in MeOH (200 mL) and (trimethylsilyl)diazomethane (2.0 M solution in hexanes, 20 mL) is added over several minutes. The reaction mixture is stirred for one hour and concentrated under reduced pressure. The residue is partitioned between water and ethyl acetate. The ethyl acetate layer is separated and dried over MgSO4. The crude product is purified via radial chromatography using 2.5% MeOH/CH2Cl2 to afford the title compound (195 mg, 30%). ES/MS m/e 327.0 (M+2). The reaction mixture is cooled filtered the solids are washed with water and air dried The solids are dissolved in MeOH (200 mL) (trimethylsilyl)diazomethane (2.0 M solution in hexanes, 20 mL) is added over several minutes concentrated under reduced pressure The residue is partitioned between water and ethyl acetate The ethyl acetate layer is separated dried over MgSO4 The crude product is purified via radial chromatography

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

Procedure: Sodium hydride (60% in mineral oil, 87 mg, 2.2 mmol) is added to a solution of 6-bromo-1H-indole-3-carboxylic acid methyl ester (500 mg, 1.97 mmol) in DMF (5 mL) at room temperature and the mixture is stirred for 30 minutes. To the reaction mixture is added 1-bromo-2-methoxy-ethane (222 μL, 2.36 mmol). After one hour, sodium hydride (20 mg) is added. Thirty minutes later, 1-bromo-2-methoxy-ethane (60 μL) is added. The mixture is heated to 60° C. for one hour. The cooled mixture is quenched with a small amount of water and concentrated under reduced pressure. The residue is taken up in ethyl acetate and filtered. The filtrate is concentrated under reduced pressure and the resulting residue is purified by column chromatography (gradient: 10 to 60% ethyl acetate/heptane) followed by purification via radial chromatography (gradient: 0 to 1% MeOH/CH2Cl2) to provide the title compound (386 mg, 63%). ES/MS m/e 314.0 (M+2). After one hour The cooled mixture is quenched with a small amount of water concentrated under reduced pressure filtered The filtrate is concentrated under reduced pressure the resulting residue is purified by column chromatography (gradient: 10 to 60% ethyl acetate/heptane) followed by purification via radial chromatography (gradient: 0 to 1% MeOH/CH2Cl2)

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

Procedure: Sodium hydride (60% in mineral oil, 87 mg, 2.2 mmol) is added to a solution of 6-bromo-1H-indole-3-carboxylic acid methyl ester (500 mg, 1.97 mmol) in DMF (5 mL) at room temperature and the mixture is stirred for 30 minutes. To the reaction mixture is added 1-bromo-2-methoxy-ethane (222 μL, 2.36 mmol). After one hour, sodium hydride (20 mg) is added. Thirty minutes later, 1-bromo-2-methoxy-ethane (60 μL) is added. The mixture is heated to 60° C. for one hour. The cooled mixture is quenched with a small amount of water and concentrated under reduced pressure. The residue is taken up in ethyl acetate and filtered. The filtrate is concentrated under reduced pressure and the resulting residue is purified by column chromatography (gradient: 10 to 60% ethyl acetate/heptane) followed by purification via radial chromatography (gradient: 0 to 1% MeOH/CH2Cl2) to provide the title compound (386 mg, 63%). ES/MS m/e 314.0 (M+2). After one hour The cooled mixture is quenched with a small amount of water concentrated under reduced pressure filtered The filtrate is concentrated under reduced pressure the resulting residue is purified by column chromatography (gradient: 10 to 60% ethyl acetate/heptane) followed by purification via radial chromatography (gradient: 0 to 1% MeOH/CH2Cl2)

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

Procedure: To a solution of 6-bromoindole-3-carboxylic acid (960 mg, 4.00 mmol) in methanol (9.5 mL) is added (trimethylsilyl)diazomethane (2.0 M solution in hexanes, ca 9 mL) over two minutes at room temperature. The yellow mixture is concentrated under reduced pressure. The residue is redissolved in methanol and concentrated under reduced pressure. This process is repeated several times to give the title compound as a solid (100%). ES/MS m/e 256.0 (M+2). The yellow mixture is concentrated under reduced pressure The residue is redissolved in methanol concentrated under reduced pressure