methyl 3-cyano-1H-indole-2-carboxylate

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2 g 3-Iodo-1H-indole-2-carboxylic acid methyl ester in 10 ml DMF and 20 ml THF, 1.5 g CuCN, 434 mg Et4NCN and 461 mg DPPF were added and the mixture was purged with argon for 15 min. Then, 254 mg Pd2(dba)3 were introduced and the reaction was heated to 80° C. for 5 h. Finally, 10 ml saturated NaHCO3 solution were added and the mixture was filtered through a chem elut® cartridge by elution with DCM. After subsequent removal of the solvent under reduced pressure the residue was purified by chromatography on silica gel with ethylacetate as eluent. The fractions containing the product were evaporated to yield a white solid. Yield: 1.2 g. the mixture was purged with argon for 15 min Then, 254 mg Pd2(dba)3 were introduced Finally, 10 ml saturated NaHCO3 solution were added the mixture was filtered through a chem elut® cartridge by elution with DCM After subsequent removal of the solvent under reduced pressure the residue was purified by chromatography on silica gel with ethylacetate as eluent The fractions containing the product were evaporated to yield a white solid

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

Procedure: Activated molecular sieves (6.0 g, 27 mmol) 4 Å were placed in an oven dried flask and cooled to room temperature under nitrogen. To the flask was charged with methyl 3-cyano-1H-indole-2-carboxylate (0.45 g, 2.2 mmol), (3-fluorophenyl)boronic acid (0.94 g, 6.7 mmol), cupric acetate (0.61 g, 3.4 mmol), methylene chloride (43 mL) and pyridine (0.73 mL, 9.0 mmol). The reaction mixture was stirred at room temperature over the weekend. The mixture was filtered through a pad of Celite. The filtrate was concentrated and purified on silica gel (eluting with 0-60% EtOAc/hexane) to give the desired product (0.39 g, 59%). LCMS calculated for C17H12FN2O2(M+H)+: m/z=295.1. Found: 295.0. Activated molecular sieves (6.0 g, 27 mmol) 4 Å were placed in an oven dried flask The mixture was filtered through a pad of Celite The filtrate was concentrated purified on silica gel (eluting with 0-60% EtOAc/hexane)

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

Procedure: To a mixture of methyl 3-[(E)-(hydroxyimino)methyl]-1H-indole-2-carboxylate (from Key Organics, 1.0 g, 4.6 mmol) and pyridine (7.4 mL, 92 mmol) in 1,4-dioxane (20 mL) was added methanesulfonyl chloride (1.4 mL, 18 mmol). The reaction was heated at 60° C. for 2 hours. The reaction was diluted with water and extracted with EtOAc. The combined organic layers were dried over MgSO4, concentrated, and purified on silica gel (eluting with 0-5% MeOH/dichloromethane) to give the desired product (0.7 g, 76%). LCMS calculated for C11H9N2O2(M+H)+: m/z=201.1. Found: 201.1. extracted with EtOAc The combined organic layers were dried over MgSO4 concentrated purified on silica gel (eluting with 0-5% MeOH/dichloromethane)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2 g 3-Iodo-1H-indole-2-carboxylic acid methyl ester in 10 ml DMF and 20 ml THF, 1.5 g CuCN, 434 mg Et4NCN and 461 mg DPPF were added and the mixture was purged with argon for 15 min. Then, 254 mg Pd2(dba)3 were introduced and the reaction was heated to 80° C. for 5 h. Finally, 10 ml saturated NaHCO3 solution were added and the mixture was filtered through a chem elut® cartridge by elution with DCM. After subsequent removal of the solvent under reduced pressure the residue was purified by chromatography on silica gel with ethylacetate as eluent. The fractions containing the product were evaporated to yield a white solid. Yield: 1.2 g. the mixture was purged with argon for 15 min Then, 254 mg Pd2(dba)3 were introduced Finally, 10 ml saturated NaHCO3 solution were added the mixture was filtered through a chem elut® cartridge by elution with DCM After subsequent removal of the solvent under reduced pressure the residue was purified by chromatography on silica gel with ethylacetate as eluent The fractions containing the product were evaporated to yield a white solid