3-naphthalen-1-ylpropanal

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

Procedure: Stir a mixture of 7-phenyl-isoquinoline-5-sulfonic acid (2-amino-ethyl)-amide (0.25 mmol, 1.0 eq) and 3-naphthalen-1-yl-propionaldehyde (0.25 mmol, 1.0 eq) in 1,2-dichloroethane (DCE) (2.0 mL) at room temperature for six (6) hours, and then add sodium triacetoxyborohydride (0.6 mmol, 2.4 eq). Stir overnight, then dilute the mixture with CH3OH, and apply to a cation exchange column (10 g), wash with a mixture of, CH3OH and CH2Cl2 (1:1), then NH3 (2.0 M in CH3OH). Purify the residue on silica gel (gradient 10% CH3OH in CH2Cl2) to give 100 mg the free amine product as oil. Dissolve the free amine in CH3OH (15 mL) and treat dropwise with 37% HCl aqueous solution (1.0 mL) with stirring. Concentrate the resultant solution and dried under vacuum at 37° C. to give the title compound as a white powder. 1H NMR (DMSO-d6, 400 MHz): 9.65 (1H, s), 8.85 (2H, br), 8.75 (1H, s), 8.69 (1H, d, J=6.0 Hz), 8.64 (1H,s), 8.53 (1H, t, J=6.0 Hz), 8.07 (1H, d, J=8.0 Hz), 7.91 (2H, d, J=7.6 Hz), 7.78 (1H, d, J=8.0 Hz), 7.49-7.61(4H, s), 7.46 (1H, d, J=7.6 Hz), 7.35 (1H, d, J=7.2 Hz), 3.12-3.15 (2H, m), 3.07 (2H, t, J=7.6 Hz), 2.95-3.02 (4H, m), 1.93-1.99 (2H, m). IS-MS, m/e 582.58 (m+1) Stir overnight apply to a cation exchange column (10 g), wash with a mixture of, CH3OH and CH2Cl2 (1:1) Purify the residue on silica gel (gradient 10% CH3OH in CH2Cl2)

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

Procedure: Stir a mixture of 7-phenyl-isoquinoline-5-sulfonic acid (2-amino-ethyl)-amide (0.25 mmol, 1.0 eq) and 3-naphthalen-1-yl-propionaldehyde (0.25 mmol, 1.0 eq) in 1,2-dichloroethane (DCE) (2.0 mL) at room temperature for six (6) hours, and then add sodium triacetoxyborohydride (0.6 mmol, 2.4 eq). Stir overnight, then dilute the mixture with CH3OH, and apply to a cation exchange column (10 g), wash with a mixture of, CH3OH and CH2Cl2 (1:1), then NH3 (2.0 M in CH3OH). Purify the residue on silica gel (gradient 10% CH3OH in CH2Cl2) to give 100 mg the free amine product as oil. Dissolve the free amine in CH3OH (15 mL) and treat dropwise with 37% HCl aqueous solution (1.0 mL) with stirring. Concentrate the resultant solution and dried under vacuum at 37° C. to give the title compound as a white powder. 1H NMR (DMSO-d6, 400 MHz): 9.65 (1H, s), 8.85 (2H, br), 8.75 (1H, s), 8.69 (1H, d, J=6.0 Hz), 8.64 (1H,s), 8.53 (1H, t, J=6.0 Hz), 8.07 (1H, d, J=8.0 Hz), 7.91 (2H, d, J=7.6 Hz), 7.78 (1H, d, J=8.0 Hz), 7.49-7.61(4H, s), 7.46 (1H, d, J=7.6 Hz), 7.35 (1H, d, J=7.2 Hz), 3.12-3.15 (2H, m), 3.07 (2H, t, J=7.6 Hz), 2.95-3.02 (4H, m), 1.93-1.99 (2H, m). IS-MS, m/e 582.58 (m+1) Stir overnight apply to a cation exchange column (10 g), wash with a mixture of, CH3OH and CH2Cl2 (1:1) Purify the residue on silica gel (gradient 10% CH3OH in CH2Cl2)

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

Procedure: To a stirred solution of 3-(naphthalen-1-yl)propanal (2.3 g, 12.5 mmol) in DMF (6 mL) under nitrogen is added dibenzyl phosphite (3.3 g, 12.5 mmol), followed by potassium fluoride (0.94 g, 16.2 mmol). After 2 hours, the stirred suspension is diluted with ethyl acetate (60 mL) and washed with water (3×20 mL). The organic layer is dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue is purified by flash-chromatography on silica gel, eluting with a gradient of ethyl acetate in hexane (30% to 40% ). Concentration of the pure fractions in vacuo yields [1-hydroxy-3-(naphthalen-1-yl)-propyl]phosphonic acid dibenzyl ester as an oil which solidifies on standing. washed with water (3×20 mL) The organic layer is dried over anhydrous MgSO4 filtered concentrated in vacuo The residue is purified by flash-chromatography on silica gel eluting with a gradient of ethyl acetate in hexane (30% to 40% )

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

Procedure: Stir a mixture of 7-phenyl-isoquinoline-5-sulfonic acid (2-amino-ethyl)-amide (0.25 mmol, 1.0 eq) and 3-naphthalen-1-yl-propionaldehyde (0.25 mmol, 1.0 eq) in 1,2-dichloroethane (DCE) (2.0 mL) at room temperature for six (6) hours, and then add sodium triacetoxyborohydride (0.6 mmol, 2.4 eq). Stir overnight, then dilute the mixture with CH3OH, and apply to a cation exchange column (10 g), wash with a mixture of, CH3OH and CH2Cl2 (1:1), then NH3 (2.0 M in CH3OH). Purify the residue on silica gel (gradient 10% CH3OH in CH2Cl2) to give 100 mg the free amine product as oil. Dissolve the free amine in CH3OH (15 mL) and treat dropwise with 37% HCl aqueous solution (1.0 mL) with stirring. Concentrate the resultant solution and dried under vacuum at 37° C. to give the title compound as a white powder. 1H NMR (DMSO-d6, 400 MHz): 9.65 (1H, s), 8.85 (2H, br), 8.75 (1H, s), 8.69 (1H, d, J=6.0 Hz), 8.64 (1H,s), 8.53 (1H, t, J=6.0 Hz), 8.07 (1H, d, J=8.0 Hz), 7.91 (2H, d, J=7.6 Hz), 7.78 (1H, d, J=8.0 Hz), 7.49-7.61(4H, s), 7.46 (1H, d, J=7.6 Hz), 7.35 (1H, d, J=7.2 Hz), 3.12-3.15 (2H, m), 3.07 (2H, t, J=7.6 Hz), 2.95-3.02 (4H, m), 1.93-1.99 (2H, m). IS-MS, m/e 582.58 (m+1) Stir overnight apply to a cation exchange column (10 g), wash with a mixture of, CH3OH and CH2Cl2 (1:1) Purify the residue on silica gel (gradient 10% CH3OH in CH2Cl2)

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

Procedure: Stir a mixture of 7-phenyl-isoquinoline-5-sulfonic acid (2-amino-ethyl)-amide (0.25 mmol, 1.0 eq) and 3-naphthalen-1-yl-propionaldehyde (0.25 mmol, 1.0 eq) in 1,2-dichloroethane (DCE) (2.0 mL) at room temperature for six (6) hours, and then add sodium triacetoxyborohydride (0.6 mmol, 2.4 eq). Stir overnight, then dilute the mixture with CH3OH, and apply to a cation exchange column (10 g), wash with a mixture of, CH3OH and CH2Cl2 (1:1), then NH3 (2.0 M in CH3OH). Purify the residue on silica gel (gradient 10% CH3OH in CH2Cl2) to give 100 mg the free amine product as oil. Dissolve the free amine in CH3OH (15 mL) and treat dropwise with 37% HCl aqueous solution (1.0 mL) with stirring. Concentrate the resultant solution and dried under vacuum at 37° C. to give the title compound as a white powder. 1H NMR (DMSO-d6, 400 MHz): 9.65 (1H, s), 8.85 (2H, br), 8.75 (1H, s), 8.69 (1H, d, J=6.0 Hz), 8.64 (1H,s), 8.53 (1H, t, J=6.0 Hz), 8.07 (1H, d, J=8.0 Hz), 7.91 (2H, d, J=7.6 Hz), 7.78 (1H, d, J=8.0 Hz), 7.49-7.61(4H, s), 7.46 (1H, d, J=7.6 Hz), 7.35 (1H, d, J=7.2 Hz), 3.12-3.15 (2H, m), 3.07 (2H, t, J=7.6 Hz), 2.95-3.02 (4H, m), 1.93-1.99 (2H, m). IS-MS, m/e 582.58 (m+1) Stir overnight apply to a cation exchange column (10 g), wash with a mixture of, CH3OH and CH2Cl2 (1:1) Purify the residue on silica gel (gradient 10% CH3OH in CH2Cl2)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of L-leucyl-L-tryptophan benzyl ester (408 mg) and 3-(1-naphthyl)propionaldehyde (220 mg) in toluene (10 ml) was heated to reflux in a Dean-Stark apparatus for 2 hours. After cooling, dibenzyl phosphite (252 mg) and acetonitrile (10 ml) were added to the mixture and the resulting solution was stirred at 100° C. for 16 hours. After being cooled to room temperature, the mixture was concentrated under reduced pressure. The residue was separated and purified by silica gel chromatography (chloroform:ethyl acetate=5:1) to give two diastereomers of the title compound as colorless oil (a: 58 mg, b: 95 mg). was heated to reflux in a Dean-Stark apparatus for 2 hours After cooling After being cooled to room temperature the mixture was concentrated under reduced pressure The residue was separated purified by silica gel chromatography (chloroform:ethyl acetate=5:1)

Conditions: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 5.2 g (0.04 mole) of ethyl acetoacetate in a small quantity of anhydrous tetrahydrofuran was added dropwise to 1.2 g (0.04 mole) of sodium hydride (in the form of a 55% w/w suspension in oil) in 100 ml of anhydrious tetrahydrofuran, with ice-cooling and stirring. The mixture was then stirred for 30 minutes. after which it was cooled to a temperature of from -10° C. to -5° C. To the mixture were added dropwise 30 ml of an n-hexane solution containing 0.04 mole of n-butyllithium. The mixture was stirred at a temperature from 5° C. to 0° C. for 30 minutes, after which it was cooled to -60° C. 6 g (0.033 mole) of 3-(1-naphthyl)propionaldehyde in 50 ml of anhydrous tetrahydrofuran were then added all at once to the reaction mixture. After stirring the mixture for 30 minutes, it was poured into about 500 ml of ice-water. It was then acidified by the addition of hydrochloric acid, with stirring, and the tetrahyrofuran layer was separated. The aqueous layer was extracted three times, each time with 100 ml of ethyl acetate. The tetrahydrofuran layer and the ethyl acetate extracts were combined, washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulphate. The solvent was then evaporated off under reduced pressure. The resulting residue was adsorbed on a silica gel column chromatography and the fractions eluted with a 10:3 by volume mixture of ethyl acetate and n-hexane were evaporated to dryness to give 4.0 g (yield 30%) of ethyl 5-hydroxy-7-(1-naphthyl)-3-oxoheptanoate. with ice-cooling The mixture was then stirred for 30 minutes after which it was cooled to a temperature of from -10° C. to -5° C The mixture was stirred at a temperature from 5° C. to 0° C. for 30 minutes After stirring the mixture for 30 minutes with stirring the tetrahyrofuran layer was separated The aqueous layer was extracted three times washed with saturated aqueous sodium chloride dried over anhydrous sodium sulphate The solvent was then evaporated off under reduced pressure the fractions eluted with a 10:3 by volume mixture of ethyl acetate and n-hexane were evaporated to dryness

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

Procedure: To a stirred solution of 3-(naphthalen-1-yl)propanal (2.3 g, 12.5 mmol) in DMF (6 mL) under nitrogen is added dibenzyl phosphite (3.3 g, 12.5 mmol), followed by potassium fluoride (0.94 g, 16.2 mmol). After 2 hours, the stirred suspension is diluted with ethyl acetate (60 mL) and washed with water (3×20 mL). The organic layer is dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue is purified by flash-chromatography on silica gel, eluting with a gradient of ethyl acetate in hexane (30% to 40% ). Concentration of the pure fractions in vacuo yields [1-hydroxy-3-(naphthalen-1-yl)-propyl]phosphonic acid dibenzyl ester as an oil which solidifies on standing. washed with water (3×20 mL) The organic layer is dried over anhydrous MgSO4 filtered concentrated in vacuo The residue is purified by flash-chromatography on silica gel eluting with a gradient of ethyl acetate in hexane (30% to 40% )

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

Procedure: Stir a mixture of 7-phenyl-isoquinoline-5-sulfonic acid (2-amino-ethyl)-amide (0.25 mmol, 1.0 eq) and 3-naphthalen-1-yl-propionaldehyde (0.25 mmol, 1.0 eq) in 1,2-dichloroethane (DCE) (2.0 mL) at room temperature for six (6) hours, and then add sodium triacetoxyborohydride (0.6 mmol, 2.4 eq). Stir overnight, then dilute the mixture with CH3OH, and apply to a cation exchange column (10 g), wash with a mixture of, CH3OH and CH2Cl2 (1:1), then NH3 (2.0 M in CH3OH). Purify the residue on silica gel (gradient 10% CH3OH in CH2Cl2) to give 100 mg the free amine product as oil. Dissolve the free amine in CH3OH (15 mL) and treat dropwise with 37% HCl aqueous solution (1.0 mL) with stirring. Concentrate the resultant solution and dried under vacuum at 37° C. to give the title compound as a white powder. 1H NMR (DMSO-d6, 400 MHz): 9.65 (1H, s), 8.85 (2H, br), 8.75 (1H, s), 8.69 (1H, d, J=6.0 Hz), 8.64 (1H,s), 8.53 (1H, t, J=6.0 Hz), 8.07 (1H, d, J=8.0 Hz), 7.91 (2H, d, J=7.6 Hz), 7.78 (1H, d, J=8.0 Hz), 7.49-7.61(4H, s), 7.46 (1H, d, J=7.6 Hz), 7.35 (1H, d, J=7.2 Hz), 3.12-3.15 (2H, m), 3.07 (2H, t, J=7.6 Hz), 2.95-3.02 (4H, m), 1.93-1.99 (2H, m). IS-MS, m/e 582.58 (m+1) Stir overnight apply to a cation exchange column (10 g), wash with a mixture of, CH3OH and CH2Cl2 (1:1) Purify the residue on silica gel (gradient 10% CH3OH in CH2Cl2)