ethyl 6-chloro-3-formyl-1H-indole-2-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:; See reaction.notes.procedure_details.

Procedure: The title compound is prepared according to a published literature procedure (see J. Med. Chem. 2005, 48, 995-1018.) A solution of 6-chloro-1H-indole-2-carboxylic acid ethyl ester (5.0 g, 22.4 mmol) (commercially available from 3D Medical Systems Inc.) and POCl3 (2.46 mL, 26.8 mmol) in DMF (15 mL) is heated at 50° C. for 28 h. After completion, the reaction mixture is quenched by aqueous NaHCO3, Et2O is added and the organic layer is washed with brine, dried over MgSO4 and evaporated in vacuo. Silica gel flash chromatography of the residue affords the title compound as a colorless powder; ES-MS: M−=250.1; HPLC: AtRet=4.67 min. The title compound is prepared After completion, the reaction mixture is quenched by aqueous NaHCO3, Et2O is added the organic layer is washed with brine dried over MgSO4 evaporated in vacuo

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

Procedure: The title compound is prepared according to a published literature procedure (see J. Med. Chem. 2005, 48, 995-1018.) A solution of 6-chloro-1H-indole-2-carboxylic acid ethyl ester (5.0 g, 22.4 mmol) (commercially available from 3D Medical Systems Inc.) and POCl3 (2.46 mL, 26.8 mmol) in DMF (15 mL) is heated at 50° C. for 28 h. After completion, the reaction mixture is quenched by aqueous NaHCO3, Et2O is added and the organic layer is washed with brine, dried over MgSO4 and evaporated in vacuo. Silica gel flash chromatography of the residue affords the title compound as a colorless powder; ES-MS: M−=250.1; HPLC: AtRet=4.67 min. The title compound is prepared After completion, the reaction mixture is quenched by aqueous NaHCO3, Et2O is added the organic layer is washed with brine dried over MgSO4 evaporated in vacuo

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 commercially available 6-chloro-3-formyl-1H-indole-2-carboxylic acid ethyl ester in t-BuOH and 2-methyl-2-butene (50 eq) was added 9.2 eq NaClO2 (9 eq) and aq. NaH2PO4 (7 eq) and stirred 12 h at room temperature. After concentration the mixture was dissolved in H2O and adjusted to pH7 and then extracted with EtOAc; partial concentration of the organic phase precipitated the product in 52% yield. After concentration the mixture was dissolved in H2O extracted with EtOAc partial concentration of the organic phase precipitated the product in 52% yield

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

Procedure: To a solution of commercially available 6-chloro-3-formyl-1H-indole-2-carboxylic acid ethyl ester in t-BuOH and 2-methyl-2-butene (50 eq) was added 9.2 eq NaClO2 (9 eq) and aq. NaH2PO4 (7 eq) and stirred 12 h at room temperature. After concentration the mixture was dissolved in H2O and adjusted to pH7 and then extracted with EtOAc; partial concentration of the organic phase precipitated the product in 52% yield. After concentration the mixture was dissolved in H2O extracted with EtOAc partial concentration of the organic phase precipitated the product in 52% yield

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

Procedure: To a solution of 0.104 g (0.413 mmol) of 6-Chloro-3-formyl-1H-indole-2-carboxylic acid ethyl ester in a mixture of tert-butanol (10 ml) and H2O (5 ml), was added 2-methyl-2-butene (2 ml) followed by a solution of NaClO2 (0.344 g, 3.80 mmol) and NaH2PO4 (0.399 g, 2.90 mmol) in water (2 ml). The mixture was stirred overnight at RT. The organic solvents were removed, and then the aqueous solution diluted with water, and washed twice with hexane. The ph of the aqueous phase was adjusted to 3 by addition of aq. HCl 1N, and the product extracted with EtOAc. The combined organic phases were dried over Na2SO4 and concentrated in vacuo to afford 15 mg (14%) of 6-chloro-1H-indole-2,3-dicarboxylic acid 2-ethyl ester as alight yellow solid. The organic solvents were removed the aqueous solution diluted with water washed twice with hexane The ph of the aqueous phase was adjusted to 3 by addition of aq. HCl 1N the product extracted with EtOAc The combined organic phases were dried over Na2SO4 concentrated in vacuo

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

Procedure: To a stirred solution of 2.36 g (0.011 mol) of 6-chloro-1H-indole-2-carboxylic acid ethyl ester in DMF (20 ml) was added phosphorus oxychloride (1.08 ml, 0.012 mol) at RT. The solution was heated at 60° C. for 2 hours, then cooled to RT, and poured into water. The ph was adjusted to 7 by careful addition of aq. NaOH 2N. The resulting brown precipitate was collected by filtration and dried over night in a vacuum oven (50° C.). The title compound was obtained as light brown solid, 2.05 g (77%). cooled to RT The resulting brown precipitate was collected by filtration dried over night in a vacuum oven (50° C.)

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 0.104 g (0.413 mmol) of 6-Chloro-3-formyl-1H-indole-2-carboxylic acid ethyl ester in a mixture of tert-butanol (10 ml) and H2O (5 ml), was added 2-methyl-2-butene (2 ml) followed by a solution of NaClO2 (0.344 g, 3.80 mmol) and NaH2PO4 (0.399 g, 2.90 mmol) in water (2 ml). The mixture was stirred overnight at RT. The organic solvents were removed, and then the aqueous solution diluted with water, and washed twice with hexane. The ph of the aqueous phase was adjusted to 3 by addition of aq. HCl 1N, and the product extracted with EtOAc. The combined organic phases were dried over Na2SO4 and concentrated in vacuo to afford 15 mg (14%) of 6-chloro-1H-indole-2,3-dicarboxylic acid 2-ethyl ester as a light yellow solid. The organic solvents were removed the aqueous solution diluted with water washed twice with hexane The ph of the aqueous phase was adjusted to 3 by addition of aq. HCl 1N the product extracted with EtOAc The combined organic phases were dried over Na2SO4 concentrated in vacuo