m-(Methylamino)phenol

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

Procedure: To 3-(N-methylamino)phenol (10 g, 80 mmol), dissolved in 80 ml of NMP, was added allyl bromide (9.8 ml, 113 mmol) via syringe. The yellow solution was heated to 80° C. for 4 hours. The reaction mixture was poured into distilled water (200 ml) and saturated aqueous sodium bicarbonate solution was added. Extraction with diethyl ether (3×200 ml), drying over anhydrous magnesium sulfate, filtration and concentration vacuo yielded 18.0 g of 3-(N-allyl-N-methylamino)phenol as a viscous green tinted oil. Vacuum distillation at 1 torr (110°-120° C.) yielded 10.5 g (80%) as a pale yellow oil. The reaction mixture was poured into distilled water (200 ml) and saturated aqueous sodium bicarbonate solution was added Extraction with diethyl ether (3×200 ml) drying over anhydrous magnesium sulfate, filtration and concentration vacuo

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

Procedure: To 3-(N-methylamino)phenol (10 g, 80 mmol), dissolved in 80 ml of NMP, was added allyl bromide (9.8 ml, 113 mmol) via syringe. The yellow solution was heated to 80° C. for 4 hours. The reaction mixture was poured into distilled water (200 ml) and saturated aqueous sodium bicarbonate solution was added. Extraction with diethyl ether (3×200 ml), drying over anhydrous magnesium sulfate, filtration and concentration vacuo yielded 18.0 g of 3-(N-allyl-N-methylamino)phenol as a viscous green tinted oil. Vacuum distillation at 1 torr (110°-120° C.) yielded 10.5 g (80%) as a pale yellow oil. The reaction mixture was poured into distilled water (200 ml) and saturated aqueous sodium bicarbonate solution was added Extraction with diethyl ether (3×200 ml) drying over anhydrous magnesium sulfate, filtration and concentration vacuo

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

Procedure: This compound was obtained (yield 45%) based on the method described in Production Example 2B using 4,6-dichloro-2-methylpyrimidine instead of the 4,6-dichloro-2-ethylpyrimidine, and using 3-methylaminophenol instead of the 3-aminophenol. This compound was obtained (yield 45%)

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

Procedure: This compound was obtained (yield 45%) based on the method described in Production Example 2B using 4,6-dichloro-2-methylpyrimidine instead of the 4,6-dichloro-2-ethylpyrimidine, and using 3-methylaminophenol instead of the 3-aminophenol. This compound was obtained (yield 45%)

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

Procedure: This compound was obtained (yield 43%) based on the method described in Production Example 2B using 4,6-dichloropyrimidine instead of the 4,6-dichloro-2-ethylpyrimidine, and using 3-methylaminophenol instead of the 3-aminophenol. This compound was obtained (yield 43%)

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

Procedure: To 3- (N-methylamino) phenol (10 g, 80 mmol) , dissolved in 80 ml of NMP, was added allyl bromide (9.8 ml, 113 mmol) via syringe. The yellow solution was heated to 80° C. for 4 hours. The reaction mixture was poured into distilled water (200 ml) and saturated aqueous sodium bicarbonate solution was added. Extraction with diethyl ether (3×200 ml), drying over anhydrous magnesium sulfate, filtration and concentration in vacuo yielded 18.0 g of 3-(N-allyl-N-methylamino)phenol as a viscous green tinted oil. Vacuum distillation at 1 torr (110°-120° C.) yielded 10.5 g (80%) as a pale yellow oil. The reaction mixture was poured into distilled water (200 ml) and saturated aqueous sodium bicarbonate solution was added Extraction with diethyl ether (3×200 ml) drying over anhydrous magnesium sulfate, filtration and concentration in vacuo

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

Procedure: To 3- (N-methylamino) phenol (10 g, 80 mmol) , dissolved in 80 ml of NMP, was added allyl bromide (9.8 ml, 113 mmol) via syringe. The yellow solution was heated to 80° C. for 4 hours. The reaction mixture was poured into distilled water (200 ml) and saturated aqueous sodium bicarbonate solution was added. Extraction with diethyl ether (3×200 ml), drying over anhydrous magnesium sulfate, filtration and concentration in vacuo yielded 18.0 g of 3-(N-allyl-N-methylamino)phenol as a viscous green tinted oil. Vacuum distillation at 1 torr (110°-120° C.) yielded 10.5 g (80%) as a pale yellow oil. The reaction mixture was poured into distilled water (200 ml) and saturated aqueous sodium bicarbonate solution was added Extraction with diethyl ether (3×200 ml) drying over anhydrous magnesium sulfate, filtration and concentration in vacuo

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

Procedure: 3-Aminophenol (5.37 g, 49.2 mmol) in ethylformate (30 mL) was treated with p-toluenesulfonic acid (50 mg) and heated at reflux. After 18 hours, the volatiles were evaporated under reduced pressure. The residue was taken up in ethyl acetate and washed with 1N HCl, saturated NaHCO3, brine, dried (Na2SO4), filtered, and the filtrate concentrated under reduced pressure. The residue was dissolved in THF (25 mL) and treated with 1M borane tetrahydofuran complex (27.2 mL, 27.2 mmol) in THF. After 18 hours at ambient temperature, the mixture was carefully quenched by addition of 1N HCl. After stirring for 30 minutes, the solution was basified and extracted with ethyl acetate. The organic layer was separated, washed with brine, dried (Na2SO4), filtered, and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography (30% ethyl acetate/hexanes) to provide the title compound as a viscous yellow oil (1.72 g, 28% yield). 1H NMR (300 MHz, CDCl3) δ 7.03 (t, 1H), 6.13-6.24 (m, 2H), 6.11 (t, 1H), 4.54 (bs, 1H), 3.72 (bs, 1H), 2.82 (s, 3H); MS (DCI/NH3) 124 (M+H)+, 141 (M+NH4)+. heated at reflux the volatiles were evaporated under reduced pressure washed with 1N HCl, saturated NaHCO3, brine dried (Na2SO4) filtered the filtrate concentrated under reduced pressure The residue was dissolved in THF (25 mL) After 18 hours at ambient temperature the mixture was carefully quenched by addition of 1N HCl extracted with ethyl acetate The organic layer was separated washed with brine dried (Na2SO4) filtered the filtrate concentrated under reduced pressure The residue was purified by flash chromatography (30% ethyl acetate/hexanes)