4-(2-amino-1-hydroxyethyl)phenol

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 1 N aqueous solution of sodium hydroxide (79.1 ml, 79.1 mmol) solution was added to a solution of 5 g (26.4 mmol) of 4-(2-amino-1-hydroxyethyl)phenol in dioxane (50 ml), and the mixture was stirred at room temperature for 5 min. 2-Nitrobenzenesulfonyl chloride (14.6 g, 65.9 mmol) was added to this solution, and the mixture was stirred at room temperature for 17 hr. Dioxane as the solvent was removed under the reduced pressure, and the residue was extracted with methylene chloride. The extract was dried over anhydrous sodium sulfate and was then filtered. The filtrate was concentrated under the reduced pressure, and the residue was purified by column chromatography on silica gel (hexane:ethyl acetate=2:1) to give 13.3 g (yield 97%) of the title compound. the mixture was stirred at room temperature for 17 hr Dioxane as the solvent was removed under the reduced pressure the residue was extracted with methylene chloride The extract was dried over anhydrous sodium sulfate was then filtered The filtrate was concentrated under the reduced pressure the residue was purified by column chromatography on silica gel (hexane:ethyl acetate=2:1)

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

Procedure: A 1 N aqueous solution of sodium hydroxide (79.1 ml, 79.1 mmol) solution was added to a solution of 5 g (26.4 mmol) of 4-(2-amino-1-hydroxyethyl)phenol in dioxane (50 ml), and the mixture was stirred at room temperature for 5 min. 2-Nitrobenzenesulfonyl chloride (14.6 g, 65.9 mmol) was added to this solution, and the mixture was stirred at room temperature for 17 hr. Dioxane as the solvent was removed under the reduced pressure, and the residue was extracted with methylene chloride. The extract was dried over anhydrous sodium sulfate and was then filtered. The filtrate was concentrated under the reduced pressure, and the residue was purified by column chromatography on silica gel (hexane:ethyl acetate=2:1) to give 13.3 g (yield 97%) of the title compound. the mixture was stirred at room temperature for 17 hr Dioxane as the solvent was removed under the reduced pressure the residue was extracted with methylene chloride The extract was dried over anhydrous sodium sulfate was then filtered The filtrate was concentrated under the reduced pressure the residue was purified by column chromatography on silica gel (hexane:ethyl acetate=2:1)

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

Procedure: The same procedure as described in Example 1 was repeated, using (2-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl)acetone [Synthesis, 1001 (1988)]and 2-amino-1-(4-hydroxyphenyl)ethanol, to give crude crystals. The crude crystals were washed with ether to give crystals of Compound 31 in a yield of 47%. to give crude crystals The crude crystals were washed with ether

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

Procedure: In 15 ml of anhydrous methanol were dissolved 2.93 g (15.5 mmol) of (isochroman-1-yl)acetone [Chem. Pharm. Bull., 36, 1758 (1988)] and 1.57 g (10.3 mmol) of 2-amino-1-(4-hydroxyphenyl)ethanol [U.S. Pat. No. 2,585,988 (1952)], and the resulting solution was stirred for 3 hours at room temperature. Methanol was evaporated, and anhydrous benzene was added to the mixture, and water formed was removed off by azeotropic distillation. To the resulting mixture was added 15 ml of anhydrous methanol. Subsequently, 567 mg (15 mmol) of sodium borohydride was gradually added under ice cooling, and the resulting mixture was stirred for 3 hours at room temperature. The methanol was evaporated off, and then 10% sulfuric acid aqueous solution was added to the residue, and the mixture was washed with ether. The resulting mixture was rendered basic with the addition of saturated aqueous potassium hydrogencarbonate and then extracted with ethyl acetate. The ethyl acetate layer was washed with water and then dried over anhydrous magnesium sulfate. The solvent was evaporated off, and the residue was subjected to silica gel column chromatography (ethyl acetate :triethylamine=20:1) to give 2.8 g (83%) of crystals of Compound 1. Methanol was evaporated anhydrous benzene was added to the mixture, and water formed was removed off by azeotropic distillation To the resulting mixture was added 15 ml of anhydrous methanol the resulting mixture was stirred for 3 hours at room temperature The methanol was evaporated off 10% sulfuric acid aqueous solution was added to the residue the mixture was washed with ether The resulting mixture was rendered basic with the addition of saturated aqueous potassium hydrogencarbonate extracted with ethyl acetate The ethyl acetate layer was washed with water dried over anhydrous magnesium sulfate The solvent was evaporated off

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

Procedure: A mixture of the sodium salt of octopamine (0.65 g), and 2-(4-acetonylphenoxymethyl)-5-hydroxy-4H-pyran-4-one (1.0 g) in methanol was treated with sodium cyanoborohydride (0.3 g) and stirred at ambient temperature for 18 hours. The solvent was evaporated in vacuo. The residue was suspended in acetone and filtered, washed with acetone and then purified by column chromatography on silica using 5% methanol:chloroform as eluent-increasing to 15% methanol:chloroform after elution of fast-running impurities. This gave 2-[4-[2-[(β,4-dihydroxyphenethyl)amino]propyl]phenoxymethyl]-5-hydroxy-4H-pyran-4-one(0.4 g) as a (50:50) mixture of diastereoisomers. The solvent was evaporated in vacuo filtered washed with acetone purified by column chromatography on silica using 5% methanol chloroform as eluent-increasing to 15% methanol chloroform after elution of fast-running impurities This gave 2-[4-[2-[(β,4-dihydroxyphenethyl)amino]propyl]phenoxymethyl]-5-hydroxy-4H-pyran-4-one(0.4 g) as a (50:50) mixture of diastereoisomers

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

Procedure: A 1 N aqueous solution of sodium hydroxide (79.1 ml, 79.1 mmol) solution was added to a solution of 5 g (26.4 mmol) of 4-(2-amino-1-hydroxyethyl)phenol in dioxane (50 ml), and the mixture was stirred at room temperature for 5 min. 2-Nitrobenzenesulfonyl chloride (14.6 g, 65.9 mmol) was added to this solution, and the mixture was stirred at room temperature for 17 hr. Dioxane as the solvent was removed under the reduced pressure, and the residue was extracted with methylene chloride. The extract was dried over anhydrous sodium sulfate and was then filtered. The filtrate was concentrated under the reduced pressure, and the residue was purified by column chromatography on silica gel (hexane:ethyl acetate=2:1) to give 13.3 g (yield 97%) of the title compound. the mixture was stirred at room temperature for 17 hr Dioxane as the solvent was removed under the reduced pressure the residue was extracted with methylene chloride The extract was dried over anhydrous sodium sulfate was then filtered The filtrate was concentrated under the reduced pressure the residue was purified by column chromatography on silica gel (hexane:ethyl acetate=2:1)

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

Procedure: Tyramine (TA), octopamine (OA) and norepinephrine (NE), naturally occurring monoamines that have a similar structure to DA, were tested together with DA for their ability to inhibit 3H-DA uptake. The concentration range of an unlabeled competitive inhibitor was selected according to the expected IC50 value. The IC50 values obtained were 0.39±0.11 μM for TA, 1.92±0.28 μM for OA, 4.10±1.02 μM for DA and 22.04±2.94 μM for NE. The apparent Ki values (calculation based on Cheng et al., (1973) Biochem Pharmacol 22:3099) were 0.35±0.10 μM for TA, 1.74±0.25 μM for OA, 3.72±0.92 μM for DA and 20.04±2.67 μM for The rank order of apparent Ki on OA/TAT for potential substrates was: TA<OA<DA<NE. The IC50 values obtained

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

Procedure: Following the general method as outlined in Example 22, starting from (2S,4EZ)-1-(tert-butoxycarbonyl)-4-(methoxyimino)-2-pyrrolidinecarboxylic acid, 2′,3-dimethyl[1,1′-biphenyl]-4-carboxylic acid, and 4-[(1RS)-2-amino-1-hydroxyethyl]phenol, the title compound was obtained in 90% purity by HPLC. MS(ESI+): m/z=502.

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

Procedure: Following the general method as outlined in Example 22, starting from (2S,4EZ)-1-(tert-butoxycarbonyl)-4-(methoxyimino)-2-pyrrolidinecarboxylic acid, 2′,6′-dimethyl[1,1′-biphenyl]4-carboxylic acid, and 4-[(1RS)-2-amino-1-hydroxyethyl]phenol, the title compound was obtained in 89% purity by HPLC. MS(ESI+): m/z=502.

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

Procedure: Following the general method as outlined in Example 22, starting from (2S,4EZ)-1-(tert-butoxycarbonyl)-4-(methoxyimino)-2-pyrrolidinecarboxylic acid, [1,1′-biphenyl]-4sulfonyl chloride, and 4-[(1RS)-2-amino-1-hydroxyethyl]phenol, the title compound was obtained in 72% purity by HPLC. MS(ESI+): m/z=510.