4-amino-2-methoxyphenol

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 (2E)-3-{3-cyano-4,6-dimethyl-1-[(1S)-1,2,3,4-tetrahydronaphthalen-1-yl]-1H-pyrrolo[2,3-b]pyridin-2-yl}prop-2-enoic acid (300 mg, 0.808 mmol) in THF (3 ml) were added DMF (0.03 ml) and oxalylchloride (0.0846 ml, 0.970 mmol), the mixture was stirred at room temperature for 1 hour and the solvent was distilled off under reduced pressure. The residue was added under ice-cooling to a solution of 4-hydroxy-3-methoxyaniline (135 mg, 0.968 mmol), pyridine (0.262 ml, 3.24 mmol) and THF (3 ml), and the mixture was stirred under ice-cooling for 2 hours and at room temperature for 12 hours. The reaction solution was poured into water and extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1) to give the objective product as a solid material. the solvent was distilled off under reduced pressure The residue was added under ice- the mixture was stirred under ice- cooling for 2 hours and at room temperature for 12 hours extracted with ethyl acetate The extract was washed with water dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1)

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

Procedure: This compound was prepared from 4-nitro-2-methoxyphenol (10.0 g, 59.1 mmol) in the manner described for 4-amino-3-fluorophenol, affording 5.20 g (56.9%) of 4-amino-2-methoxyphenol as a dark brown solid. 1H-NMR (DMSO-d6) δ 7.79 (br s, 1H), 6.44 (d, J=8.1 Hz, 1H), 6.21 (d, J=2.4 Hz, 1H), 5.97 (dd, J=8.4, 2.4 Hz, 1H), 4.43 (br s, 2H), 3.65 (s, 3H); TLC (66% EtOAc/Hex), Rf=0.42.

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

Procedure: 6.85 g of 1,3-dimethyl-5-ethoxycarbonylbarbituric acid and 4.2 g of 4-hydroxy-3-methoxyaniline are suspended in 60 ml of toluene, and the suspension is heated under reflux for 3 hours, whereupon ethanol escapes. On cooling to room temperature a precipitate forms which is isolated by filtration, washed with ethanol and dried. Yield: 8.3 g (86% of theory). Melting point: 252°-253° C. the suspension is heated is isolated by filtration washed with ethanol dried

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

Procedure: 6.85 g of 1,3-dimethyl-5-ethoxycarbonylbarbituric acid and 4.2 g of 4-hydroxy-3-methoxyaniline are suspended in 60 ml of toluene, and the suspension is heated under reflux for 3 hours, whereupon ethanol escapes. On cooling to room temperature a precipitate forms which is isolated by filtration, washed with ethanol and dried. Yield: 8.3 g (86% of theory). Melting point: 252°-253° C. the suspension is heated is isolated by filtration washed with ethanol dried