2,2-diethoxy-N-(naphthalen-1-ylmethyl)ethanamine

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

Procedure: To a solution of (S)-3-(4-(benzyloxy)phenyl)-2-(2-(3-(3-benzylureido)propanoyl)-1-methylhydrazinyl)propanoic acid (Compound VII-1) 126 mg (0.25 mmol) in dichloromethane 1.5 ml, 2,2-diethoxy-N-(naphthalen-1-ylmethyl)ethanamine (Compound IV-2) 85 mg (0.31 mmol) and DMT-MM 173 mg (0.63 mmol) were added and the mixture was stirred at room temperature for 3 hr. The reaction mixture was diluted with chloroform 50 ml and washed with water 50 ml twice and brine 50 ml twice and dried over magnesium sulfate and filtered. The mother solution was concentrated in vacuo and the residue was purified on silica gel column chromatography (Merck 60N spherical, neutral 10 ml elution by chloroform:methanol=100:0 to 90:10, each elution 50 ml) to give the desired product as pale yellow oil 85.0 mg (35.8%). washed with water 50 ml twice brine 50 ml twice and dried over magnesium sulfate filtered The mother solution was concentrated in vacuo the residue was purified on silica gel column chromatography (Merck 60N spherical neutral 10 ml elution by chloroform methanol=100:0 to 90:10, each elution 50 ml)

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

Procedure: According to the procedure described in the synthesis method of Compound III-1, 2,2-diethoxy-N-(naphthalen-1-ylmethyl)ethanamine (Compound IX-2) (2.73 g, 10 mmol) was coupled with (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-(4-tert-butoxyphenyl)propanoic acid (6.89 g, 15 mmol) and the obtained residue was purified by silica gel column chromatography (eluent: n-hexane:ethyl acetate=8:2 to 6:4) to obtain the title compound (6.46 g, 90%). the obtained residue was purified by silica gel column chromatography (eluent: n-hexane:ethyl acetate=8:2 to 6:4)

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

Procedure: To a solution of 1-naphthaldehyde (2.2 ml, 16.0 mmol) in tetrahydrofuran (6 ml) was added 2,2-diethoxyethanamine (2.9 ml, 20.0 mmol) and the mixture was stirred at room temperature 0.5 hr. And then sodium triacetoxyborohydride (10.6 g, 50 mmol) was added and the mixture was stirred for additional 4 hr. The reaction mixture was diluted with ethyl acetate (200 ml) and washed with saturated aqueous sodium bicarbonate (200 ml), water (200 ml) and brine (200 ml). The organic layer was dried over magnesium sulfate (5 g) and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography (eluent: n-hexane:ethyl acetate=100:0 to 70:30) to obtain the title compound (3.0 g, 46%). the mixture was stirred for additional 4 hr washed with saturated aqueous sodium bicarbonate (200 ml), water (200 ml) and brine (200 ml) The organic layer was dried over magnesium sulfate (5 g) filtered The filtrate was concentrated in vacuo the residue was purified by silica gel column chromatography (eluent: n-hexane:ethyl acetate=100:0 to 70:30)

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

Procedure: To a solution of 1-naphthaldehyde (2.2 ml, 16.0 mmol) in tetrahydrofuran (6 ml) was added 2,2-diethoxyethanamine (2.9 ml, 20.0 mmol) and the mixture was stirred at room temperature 0.5 hr. And then sodium triacetoxyborohydride (10.6 g, 50 mmol) was added and the mixture was stirred for additional 4 hr. The reaction mixture was diluted with ethyl acetate (200 ml) and washed with saturated aqueous sodium bicarbonate (200 ml), water (200 ml) and brine (200 ml). The organic layer was dried over magnesium sulfate (5 g) and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography (eluent: n-hexane:ethyl acetate=100:0 to 70:30) to obtain the title compound (3.0 g, 46%). the mixture was stirred for additional 4 hr washed with saturated aqueous sodium bicarbonate (200 ml), water (200 ml) and brine (200 ml) The organic layer was dried over magnesium sulfate (5 g) filtered The filtrate was concentrated in vacuo the residue was purified by silica gel column chromatography (eluent: n-hexane:ethyl acetate=100:0 to 70:30)

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

Procedure: According to the procedure described in the synthesis method of Compound III-1, 2,2-diethoxy-N-(naphthalen-1-ylmethyl)ethanamine (Compound IX-2) (2.73 g, 10 mmol) was coupled with (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-(4-tert-butoxyphenyl)propanoic acid (6.89 g, 15 mmol) and the obtained residue was purified by silica gel column chromatography (eluent: n-hexane:ethyl acetate=8:2 to 6:4) to obtain the title compound (6.46 g, 90%). the obtained residue was purified by silica gel column chromatography (eluent: n-hexane:ethyl acetate=8:2 to 6:4)

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

Procedure: According to the procedure described in the synthesis method of Compound III-1, 2,2-diethoxy-N-(naphthalen-1-ylmethyl)ethanamine (Compound IX-2) (2.73 g, 10 mmol) was coupled with (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-(4-tert-butoxyphenyl)propanoic acid (6.89 g, 15 mmol) and the obtained residue was purified by silica gel column chromatography (eluent: n-hexane:ethyl acetate=8:2 to 6:4) to obtain the title compound (6.46 g, 90%). the obtained residue was purified by silica gel column chromatography (eluent: n-hexane:ethyl acetate=8:2 to 6:4)

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

Procedure: To a solution of 1-naphthaldehyde (2.2 ml, 16.0 mmol) in tetrahydrofuran (6 ml) was added 2,2-diethoxyethanamine (2.9 ml, 20.0 mmol) and the mixture was stirred at room temperature 0.5 hr. And then sodium triacetoxyborohydride (10.6 g, 50 mmol) was added and the mixture was stirred for additional 4 hr. The reaction mixture was diluted with ethyl acetate (200 ml) and washed with saturated aqueous sodium bicarbonate (200 ml), water (200 ml) and brine (200 ml). The organic layer was dried over magnesium sulfate (5 g) and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography (eluent: n-hexane:ethyl acetate=100:0 to 70:30) to obtain the title compound (3.0 g, 46%). the mixture was stirred for additional 4 hr washed with saturated aqueous sodium bicarbonate (200 ml), water (200 ml) and brine (200 ml) The organic layer was dried over magnesium sulfate (5 g) filtered The filtrate was concentrated in vacuo the residue was purified by silica gel column chromatography (eluent: n-hexane:ethyl acetate=100:0 to 70:30)

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

Procedure: To a solution of 1-naphthaldehyde (2.2 ml, 16.0 mmol) in tetrahydrofuran (6 ml) was added 2,2-diethoxyethanamine (2.9 ml, 20.0 mmol) and the mixture was stirred at room temperature 0.5 hr. And then sodium triacetoxyborohydride (10.6 g, 50 mmol) was added and the mixture was stirred for additional 4 hr. The reaction mixture was diluted with ethyl acetate (200 ml) and washed with saturated aqueous sodium bicarbonate (200 ml), water (200 ml) and brine (200 ml). The organic layer was dried over magnesium sulfate (5 g) and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography (eluent: n-hexane:ethyl acetate=100:0 to 70:30) to obtain the title compound (3.0 g, 46%). the mixture was stirred for additional 4 hr washed with saturated aqueous sodium bicarbonate (200 ml), water (200 ml) and brine (200 ml) The organic layer was dried over magnesium sulfate (5 g) filtered The filtrate was concentrated in vacuo the residue was purified by silica gel column chromatography (eluent: n-hexane:ethyl acetate=100:0 to 70:30)

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

Procedure: To a solution of (S)-3-(4-(benzyloxy)phenyl)-2-(2-(3-(3-benzylureido)propanoyl)-1-methylhydrazinyl)propanoic acid (Compound VII-1) 126 mg (0.25 mmol) in dichloromethane 1.5 ml, 2,2-diethoxy-N-(naphthalen-1-ylmethyl)ethanamine (Compound IV-2) 85 mg (0.31 mmol) and DMT-MM 173 mg (0.63 mmol) were added and the mixture was stirred at room temperature for 3 hr. The reaction mixture was diluted with chloroform 50 ml and washed with water 50 ml twice and brine 50 ml twice and dried over magnesium sulfate and filtered. The mother solution was concentrated in vacuo and the residue was purified on silica gel column chromatography (Merck 60N spherical, neutral 10 ml elution by chloroform:methanol=100:0 to 90:10, each elution 50 ml) to give the desired product as pale yellow oil 85.0 mg (35.8%). washed with water 50 ml twice brine 50 ml twice and dried over magnesium sulfate filtered The mother solution was concentrated in vacuo the residue was purified on silica gel column chromatography (Merck 60N spherical neutral 10 ml elution by chloroform methanol=100:0 to 90:10, each elution 50 ml)