methyl 5-hydroxy-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:

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

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

Procedure: 5-Hydroxy-1H-indole-2-carboxylic acid methyl ester (0.845 g, 4.42 mmol) and 2-chloro-5-nitropyridine (0.771 g, 4.86 mmol) were dissolved in DMF (5 mL). To the solution was added anhydrous potassium carbonate (0.611 g, 4.42 mmol) and the resulting solution was stirred for 18 hours at 80° C. Water (80 mL) was added to the reaction solution and the mixture was extracted with ethyl acetate (80 mL). The organic layer was washed with brine, dried over anhydrous sodium sulfate and the solvent was removed by evaporation. The residue was purified by silica gel column chromatography (AcOEt:n-hexane=1:3), then the obtained solid was recrystallized from ethyl acetate and n-hexane to yield 0.753 g of the title compound as a yellow powder. the mixture was extracted with ethyl acetate (80 mL) The organic layer was washed with brine dried over anhydrous sodium sulfate the solvent was removed by evaporation The residue was purified by silica gel column chromatography (AcOEt:n-hexane=1:3) the obtained solid was recrystallized from ethyl acetate and n-hexane

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

Procedure: A 4 N hydrogen chloride-methanol solution (80 mL) of 5-hydroxyindole-2-carboxylic acid (3.0 g) was heated overnight under reflux. The solvent was evaporated off from the reaction liquid under reduced pressure, aqueous saturated sodium hydrogencarbonate solution was added to the resulting residue, and extracted with ethyl acetate. The organic layer was dried with anhydrous magnesium sulfate, and the solvent was evaporated off under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane/ethyl acetate=4/1 to 3/2) to obtain methyl 5-hydroxy-1H-indole-2-carboxylate (2.3 g) as a pale brown solid. under reflux The solvent was evaporated off from the reaction liquid under reduced pressure, aqueous saturated sodium hydrogencarbonate solution was added to the resulting residue extracted with ethyl acetate The organic layer was dried with anhydrous magnesium sulfate the solvent was evaporated off under reduced pressure The resulting residue was purified through silica gel column chromatography (hexane/ethyl acetate=4/1 to 3/2)

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

Procedure: 2-Chloromethylpyridine hydrochloride (515 mg) and methyl 5-hydroxy-1H-indole-2-carboxylate (600 mg) were processed in the same manner as in Production Example 1-1 to obtain the entitled compound (160 mg).

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

Procedure: 2-Chloromethylpyridine hydrochloride (515 mg) and methyl 5-hydroxy-1H-indole-2-carboxylate (600 mg) were processed in the same manner as in Production Example 1-1 to obtain the entitled compound (160 mg).

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 was prepared using the procedure of example 69 using 5-Hydroxy-1H-indole-2-carboxylic acid methyl ester as the phenol and [3-(3-Benzyl-8-trifluoromethyl-quinolin-4-yl)-phenyl]-methanol as the alcohol. MS (ESI) m/z 553.