2,6-dimethoxyaniline

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

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

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 78 (170 mg, 0.93 mmol) in AcOH (5 mL), EtOH (5 mL) and H2O (2.5 mL) was added iron powder (311 mg, ˜325 mesh, 5.57 mmol) portion wise. The mixture was then heated at 90° C. under N2 overnight. After cooling to room temperature, the mixture was poured onto ice, basified using solid Na2CO3 and extracted with EtOAc (3×). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to yield 79 as a pale yellow solid (139 mg, 98%). MS (APCI): m/z 154 (100%, [M+H]+) which was used in the next step without further purification. After cooling to room temperature the mixture was poured onto ice extracted with EtOAc (3×) The combined organic layers were washed with brine dried over Na2SO4 concentrated in vacuo

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

Procedure: 25 g of 2,6-dimethoxyaniline were added to a solution of 35 g of alloxan tetrahydrate in 120 ml of water. While stirring vigorously, the initially heterogeneous mixture changed after one hour into a brown solution from which grey crystals separated after a short time. The reaction mixture was stirred at room temperature for an additional 24 hours until dimethoxyaniline was no longer detectable according to thin-layer chromatography (cyclohexane/ethyl acetate/water=60:30:1). The reaction mixture was suction filtered, the residue on the suction filter was suspended with 4 portions of water to 80 ml and sucked dry. The solid was dried at 100°/16 mbar for 16 hours. There were obtained 44.2 g of 5-(4-amino-3,5-dimethoxyphenyl)-5-hydroxybarbituric acid as a light grey powder of m.p. 240°-243° (under decomposition). For purification, the powder can be recrystallized from 1-butanol, there being obtained a product of m.p. 242°-244° (decomposition). separated after a short time The reaction mixture was stirred at room temperature for an additional 24 hours until dimethoxyaniline filtered the residue on the suction filter sucked dry The solid was dried at 100°/16 mbar for 16 hours

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

Procedure: A solution of 3-(2-methylphenyl)-6,7-dihydro-5H-indeno[5,6-b]furan-2-carboxylic acid (3 g), triethylamine (2.2 ml) and DPPA (2.9 ml) in benzene (200 ml) was stirred at room temperature for 1 hour, and then heated under reflux for 1 hour. After cooling to room temperature, to the reaction solution 2,6-dimethoxyaniline (1.6 g) was added and then heated under reflux for 1 hour. The reaction solution was combined with water and chloroform, and the organic layer was washed with diluted hydrochloric acid followed by a saturated aqueous solution of sodium hydrogen carbonate and water, and after drying over magnesium sulfate, the solvent was distilled off under reduced pressure. The resultant residue was purified by a silica gel column chromatography (eluent: chloroform), and further purified by recrystallization from THF-chloroform to obtain the title compound as a colorless crystal (2.4 g, 53%). heated under reflux for 1 hour was added heated under reflux for 1 hour the organic layer was washed with diluted hydrochloric acid after drying over magnesium sulfate the solvent was distilled off under reduced pressure The resultant residue was purified by a silica gel column chromatography (eluent: chloroform) further purified by recrystallization from THF-chloroform

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: A mixture of 10.04 g (49 mmol) of 5-[(dimethylamino)methyl]uracil hydrochloride (B. Roth, J. Z. Strelitz, and B. S. Rauckman, J. Med. Chem. 23, 379 (1980) and 7.48 g (49 mmol) of 2,6-dimethoxyaniline (m.p. 73°-74.5°; prepared from 2,6-dimethoxybenzoic acid by the procedure in Org. Reactions 3, 330 (1946)) in 50 mL of ethylene glycol under nitrogen was heated at 145° for 5 hours. The mixture was cooled and the precipitated solid was collected, suspended in 300 mL of boiling ethanol and collected to give 3.91 g (29%) of the title compound; m.p. 243°-245° (dec.). The mixture was cooled the precipitated solid was collected collected

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

Procedure: A mixture of 2,4-diamino-5-hydroxymethylpyrimidine (4.30 g, 30.0 mmol), prepared from 2,4-diamino-5-cyanopyrimidine as described in U.K. Pat. No. 1 413 472, 2,6-dimethoxyaniline (5.05 g, 33.0 mmol), acetic acid (60 mL), and concentrated hydrochloric acid (4.2 mL) was refluxed for 41/2 hours, cooled, and filtered to give the hydrochloride salt of the title compound (7.13 g, 76.2%). The salt was dissolved in water and the solution made basic with concentrated ammonium hydroxide. The resulting precipitate was filtered, washed with water, and dried to give the title compound (5.18 g, 62.7%). cooled filtered

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 78 (170 mg, 0.93 mmol) in AcOH (5 mL), EtOH (5 mL) and H2O (2.5 mL) was added iron powder (311 mg, ˜325 mesh, 5.57 mmol) portion wise. The mixture was then heated at 90° C. under N2 overnight. After cooling to room temperature, the mixture was poured onto ice, basified using solid Na2CO3 and extracted with EtOAc (3×). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to yield 79 as a pale yellow solid (139 mg, 98%). MS (APCI): m/z 154 (100%, [M+H]+) which was used in the next step without further purification. After cooling to room temperature the mixture was poured onto ice extracted with EtOAc (3×) The combined organic layers were washed with brine dried over Na2SO4 concentrated in vacuo

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 78 (170 mg, 0.93 mmol) in AcOH (5 mL), EtOH (5 mL) and H2O (2.5 mL) was added iron powder (311 mg, ˜325 mesh, 5.57 mmol) portion wise. The mixture was then heated at 90° C. under N2 overnight. After cooling to room temperature, the mixture was poured onto ice, basified using solid Na2CO3 and extracted with EtOAc (3×). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to yield 79 as a pale yellow solid (139 mg, 98%). MS (APCI): m/z 154 (100%, [M+H]+) which was used in the next step without further purification. After cooling to room temperature the mixture was poured onto ice extracted with EtOAc (3×) The combined organic layers were washed with brine dried over Na2SO4 concentrated in vacuo

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

Procedure: 25 g of 2,6-dimethoxyaniline were added to a solution of 35 g of alloxan tetrahydrate in 120 ml of water. While stirring vigorously, the initially heterogeneous mixture changed after one hour into a brown solution from which grey crystals separated after a short time. The reaction mixture was stirred at room temperature for an additional 24 hours until dimethoxyaniline was no longer detectable according to thin-layer chromatography (cyclohexane/ethyl acetate/water=60:30:1). The reaction mixture was suction filtered, the residue on the suction filter was suspended with 4 portions of water to 80 ml and sucked dry. The solid was dried at 100°/16 mbar for 16 hours. There were obtained 44.2 g of 5-(4-amino-3,5-dimethoxyphenyl)-5-hydroxybarbituric acid as a light grey powder of m.p. 240°-243° (under decomposition). For purification, the powder can be recrystallized from 1-butanol, there being obtained a product of m.p. 242°-244° (decomposition). separated after a short time The reaction mixture was stirred at room temperature for an additional 24 hours until dimethoxyaniline filtered the residue on the suction filter sucked dry The solid was dried at 100°/16 mbar for 16 hours