(2S)-1-phenylpropan-2-amine

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

Procedure: Male Sprague-Dawley rats were provided water ad libitum, fasted overnight, and dosed by oral gavage with 1.5, 3, 6, 12, and 60 mg/kg of amphetamine sulfate or L-lysine-d-amphetamine containing the equivalent amounts of d-amphetamine. Concentrations of d-amphetamine were measured by ELISA.

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

Procedure: Male Sprague-Dawley rats were provided water ad libitum, fasted overnight, and dosed by oral gavage with 1.5, 3, 6, 12, and 60 mg/kg of amphetamine sulfate or L-lysine-d-amphetamine containing the equivalent amounts of d-amphetamine. Concentrations of d-amphetamine were measured by ELISA.

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

Procedure: O-Acetyl-l-carnitine·Cl (1.000 g, 4.17 mmol) was dissolved in 12.5 mL of a mixture of DMF/dioxane/water (2:2:1). NHS (0.528 g, 4.59 mmol) and DCC (0.947 g, 4.59 mmol) were added and the mixture was stirred overnight at ambient temperature. Solvents were evaporated and the remaining residue was dried overnight in high vacuum. The crude succinimidyl ester intermediate was dissolved in 20 mL of anhydrous DMF. Amphetamine sulfate (0.700 g, 1.90 mmol) and NMM (0.92 mL, 8.34 mmol) were added and the mixture stirred overnight. Solvent was evaporated to dryness and the remaining residue was leached with IPA. Solvent was evaporated to yield Carn-d-amphetamine. Solvents were evaporated the remaining residue was dried overnight in high vacuum The crude succinimidyl ester intermediate was dissolved in 20 mL of anhydrous DMF the mixture stirred overnight Solvent was evaporated to dryness Solvent was evaporated

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

Procedure: To a solution of (S)-1-phenylpropan-2-amine (0.500 g, 3698 μmol) in benzene (5 mL) was added 4-iodobenzaldehyde (858 mg, 3698 μmol) and MgSO4 (1.000 g, 8308 μmol) and the suspension stirred at RT 4 h. The suspension was filtered and the solid washed with benzene (2×2 mL). The combined filtrates were concentrated to give (S)—N-(4-iodobenzylidene)-1-phenylpropan-2-amine as a yellow oil which was used without purification in the next step. The suspension was filtered the solid washed with benzene (2×2 mL) The combined filtrates were concentrated

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

Procedure: To a solution of (S)-1-phenylpropan-2-amine (323 mg, 2389 μmol) in benzene (5 mL) was added 4-bromobenzaldehyde (442 mg, 2389 μmol and MgSO4 (500 mg, 4154 μmol) and the suspension was stirred at RT 4 h. The suspension was filtered and the solid washed with benzene (2×2 mL). The combined filtrates were concentrated to give (S)—N-(4-bromobenzylidene)-1-phenylpropan-2-amine which was used without purification in the next step. The suspension was filtered the solid washed with benzene (2×2 mL) The combined filtrates were concentrated

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

Procedure: To a solution of (S)-1-phenylpropan-2-amine (626 mg, 4630 μmol) in benzene (10 mL) was added 4-chlorobenzaldehyde (651 mg, 4630 μmol) and MgSO4 (1000 mg, 8308 μmol) and the suspension stirred at RT 4 h. The suspension was filtered and the solid washed with benzene (2×2 mL). The combined filtrates were concentrated to give (S)—N-(4-chlorobenzylidene)-1-phenylpropan-2-amine, which was carried on into the next step without purification. The suspension was filtered the solid washed with benzene (2×2 mL) The combined filtrates were concentrated

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

Procedure: To a solution of (S)-1-phenylpropan-2-amine (626 mg, 4630 μmol) in benzene (10 mL) was added 4-chlorobenzaldehyde (651 mg, 4630 μmol) and MgSO4 (1000 mg, 8308 μmol) and the suspension stirred at RT 4 h. The suspension was filtered and the solid washed with benzene (2×2 mL). The combined filtrates were concentrated to give (S)—N-(4-chlorobenzylidene)-1-phenylpropan-2-amine, which was carried on into the next step without purification. The suspension was filtered the solid washed with benzene (2×2 mL) The combined filtrates were concentrated

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

Procedure: Dextro amphetamine (200 g) and triethylamine (164 g) were dissolved in 1500 ml. of benzene. A solution of p-toluene sulfonyl chloride (310g) in 500 ml. of benzene was added dropwise to the cooled solution during one hour. The reaction mixture was stirred for three hours at room temperature, then allowed to stand for approximately 16 hours (over night) at room temperature (approximately 20° C.). The salts were filtered off and the benzene solution was washed with dilute HCl, water and brine. Evaporation of the solvent afforded an oil. to stand for approximately 16 hours at room temperature (approximately 20° C.) The salts were filtered off the benzene solution was washed with dilute HCl, water and brine Evaporation of the solvent afforded an oil

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

Procedure: Combine the acetonide (2) (638 mg, 1.87 mmol) with D-(+)-amphetamine (4.5 g) and heat to 130° C. for 5 hours under nitrogen with stirring. After cooling, purify by flash chromatography (3% to 5% to 10% methanol/chloroform) followed by radial chromatography four times (2% to 4% to 6% to 8% to 10% methanol/chloroform, 4 mm plate) to provide the secondary amine (3) (0.56 g). After cooling purify by flash chromatography (3% to 5% to 10% methanol/chloroform)

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In Scheme A, step b, the acetonide (2) is then treated with an appropriately substituted primary amine to provide the secondary amine of structure (3). More specifically, the acetonide (2) is combined with a large excess of an appropriately substituted primary amine, such as L-(-)-amphetamine, D-(+)-amphetamine, (R)-1-phenylpropylamine or (S)-1-phenylpropylamine, under an atmosphere of an inert gas such as nitrogen. The mixture is then heated to approximately 130° C. with stirring for approximately 3 to 6 hours. After cooling, the product can be isolated and purified by techniques well known to one skilled in the art. For example, the crude mixture can be directly purified by flash chromatography followed by radial chromatography using an appropriate eluent such as 3% to 6% methanol/chloroform to provide the secondary amine (3). After cooling the product can be isolated purified by techniques

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

Procedure: Dextro amphetamine (200 g) and triethylamine (164 g) were dissolved in 1500 ml. of benzene. A solution of p-toluene sulfonyl chloride (310g) in 500 ml. of benzene was added dropwise to the cooled solution during one hour. The reaction mixture was stirred for three hours at room temperature, then allowed to stand for approximately 16 hours (over night) at room temperature (approximately 20° C.). The salts were filtered off and the benzene solution was washed with dilute HCl, water and brine. Evaporation of the solvent afforded an oil. to stand for approximately 16 hours at room temperature (approximately 20° C.) The salts were filtered off the benzene solution was washed with dilute HCl, water and brine Evaporation of the solvent afforded an oil

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

Procedure: Combine the acetonide (2) (638 mg, 1.87 mmol) with D-(+)-amphetamine (4.5 g) and heat to 130° C. for 5 hours under nitrogen with stirring. After cooling, purify by flash chromatography (3% to 5% to 10% methanol/chloroform) followed by radial chromatography four times (2% to 4% to 6% to 8% to 10% methanol/chloroform, 4 mm plate) to provide the secondary amine (3) (0.56 g). After cooling purify by flash chromatography (3% to 5% to 10% methanol/chloroform)