(3-乙基苯基)甲胺

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: [2-(3-Benzyloxy-5-fluoro-phenyl)-1-oxiranyl-ethyl]-carbamic acid tert-butyl ester (3.33 g, 8.59 mmol) and m-ethyl benzylamine (2.32 g, 17.19 mmol) were dissolved in isopropyl alcohol (80 ml) and brought to reflux for 2 h. Reaction mixture was then concentrated in vacuo to remove isopropyl alcohol. Dissolved yellow liquid in ethyl acetate (30 ml), then washed with 1N HCl (3×100 ml). Aqueous layers were combined then extracted with ethyl acetate (2×100 ml). Organic layers were washed with 10% sodium bicarbonate (aq., 3×100 ml), followed by a brine wash. Organic layer was dried over sodium sulfate, filtered, then concentrated in vacuo, yielding the product (4.31 g). (ES+: 523.9) to reflux for 2 h Reaction mixture was then concentrated in vacuo to remove isopropyl alcohol Dissolved yellow liquid in ethyl acetate (30 ml) washed with 1N HCl (3×100 ml) Aqueous layers were combined then extracted with ethyl acetate (2×100 ml) Organic layers were washed with 10% sodium bicarbonate (aq., 3×100 ml) wash Organic layer was dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: tert-Butyl (1S)-2-(cyclohexyl)-1-[(2S)-oxiran-2-yl]ethylcarbamate (225 mg, 0.84 mmol) was refluxed with m-ethyl benzylamine (254 mg, 1.9 mmol) in 5 mL of isopropanol under nitrogen for 1.5 h, the solvent was removed in vacuo, and the residue was dissolved in ethyl acetate. It was washed three times with small portions of 10% HCl, and the aqueous phases were back-extracted with ethyl acetate. The combined organic phases were washed with 1 N NaHCO3 and brine, dried over Na2SO4, and concentrated. The resulting oil (300 mg) was dissolved in 2 mL of dichloromethane and 2 mL of TFA and stirred for 30 min. It was concentrated, and by weight determined to contain 4 eq. of TFA. This was dissolved in 2 mL of dry THF, and 0.4 mL (3.6 mmol) of 4-methyl morpholine was added. This was cooled to −30° C., and a mixture of 3-[(dipropylamino)carbonyl]-5-methylbenzoic acid (238 mg, 0.9 mmol) and CDI (165 mg, 1 mmol) in 3 mL of dry THF, which had previously been stirred together for 1 h at room temperature, was added. The mixture was allowed to warm to ambient temperature. After 3 days the reaction was quenched with 1 N KH2PO4 and dissolved in ethyl acetate. The organic phase was washed with 1 N KH2PO4, 1 N NaHCO3 (2×) and brine, dried over Na2SO4, and concentrated. Chromatography over silica gel, eluting with 4% to 10% methanol (containing 1% NH4OH) in dichloromethane afforded 124 mg (0.21 mmol) of N1-{(1S,2R)-1-(cyclohexylmethyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N3,N3-dipropylisophthalamide hydrochloride (EXAMPLE SP-256) as a white solid after formation of the salt with ethereal HCl: CI MS m/z 550 [M+H]+. the solvent was removed in vacuo the residue was dissolved in ethyl acetate It was washed three times with small portions of 10% HCl the aqueous phases were back-extracted with ethyl acetate The combined organic phases were washed with 1 N NaHCO3 and brine dried over Na2SO4 concentrated The resulting oil (300 mg) was dissolved in 2 mL of dichloromethane It was concentrated had previously been stirred together for 1 h at room temperature was added to warm to ambient temperature After 3 days the reaction was quenched with 1 N KH2PO4 dissolved in ethyl acetate The organic phase was washed with 1 N KH2PO4, 1 N NaHCO3 (2×) and brine dried over Na2SO4 concentrated Chromatography over silica gel, eluting with 4% to 10% methanol (containing 1% NH4OH) in dichloromethane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: [2-(3-Benzyloxy-5-fluoro-phenyl)-1-oxiranyl-ethyl]-carbamic acid tert-butyl ester (3.33 g, 8.59 mmol) and m-ethyl benzylamine (2.32 g, 17.19 mmol) were dissolved in isopropyl alcohol (80 ml) and brought to reflux for 2 h. Reaction mixture was then concentrated in vacuo to remove isopropyl alcohol. Dissolved yellow liquid in ethyl acetate (30 ml), then washed with 1N HCl (3×100 ml). Aqueous layers were combined then extracted with ethyl acetate (2×100 ml). Organic layers were washed with 10% sodium bicarbonate (aq., 3×100 ml), followed by a brine wash. Organic layer was dried over sodium sulfate, filtered, then concentrated in vacuo, yielding the product (4.31 g). (ES+: 523.9) to reflux for 2 h Reaction mixture was then concentrated in vacuo to remove isopropyl alcohol Dissolved yellow liquid in ethyl acetate (30 ml) washed with 1N HCl (3×100 ml) Aqueous layers were combined then extracted with ethyl acetate (2×100 ml) Organic layers were washed with 10% sodium bicarbonate (aq., 3×100 ml) wash Organic layer was dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: [2-(3-Benzyloxy-5-fluoro-phenyl)-1-oxiranyl-ethyl]-carbamic acid tert-butyl ester (3.33 g, 8.59 mmol) and m-ethyl benzylamine (2.32 g, 17.19 mmol) were dissolved in isopropyl alcohol (80 ml) and brought to reflux for 2 h. Reaction mixture was then concentrated in vacuo to remove isopropyl alcohol. Dissolved yellow liquid in ethyl acetate (30 ml), then washed with 1N HCl (3×100 ml). Aqueous layers were combined then extracted with ethyl acetate (2×100 ml). Organic layers were washed with 10% sodium bicarbonate (aq., 3×100 ml), followed by a brine wash. Organic layer was dried over sodium sulfate, filtered, then concentrated in vacuo, yielding the product (4.31 g). (ES+: 523.9) to reflux for 2 h Reaction mixture was then concentrated in vacuo to remove isopropyl alcohol Dissolved yellow liquid in ethyl acetate (30 ml) washed with 1N HCl (3×100 ml) Aqueous layers were combined then extracted with ethyl acetate (2×100 ml) Organic layers were washed with 10% sodium bicarbonate (aq., 3×100 ml) wash Organic layer was dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: tert-Butyl (1S)-2-(cyclohexyl)-1-[(2S)-oxiran-2-yl]ethylcarbamate (225 mg, 0.84 mmol) was refluxed with m-ethyl benzylamine (254 mg, 1.9 mmol) in 5 mL of isopropanol under nitrogen for 1.5 h, the solvent was removed in vacuo, and the residue was dissolved in ethyl acetate. It was washed three times with small portions of 10% HCl, and the aqueous phases were back-extracted with ethyl acetate. The combined organic phases were washed with 1 N NaHCO3 and brine, dried over Na2SO4, and concentrated. The resulting oil (300 mg) was dissolved in 2 mL of dichloromethane and 2 mL of TFA and stirred for 30 min. It was concentrated, and by weight determined to contain 4 eq. of TFA. This was dissolved in 2 mL of dry THF, and 0.4 mL (3.6 mmol) of 4-methyl morpholine was added. This was cooled to −30° C., and a mixture of 3-[(dipropylamino)carbonyl]-5-methylbenzoic acid (238 mg, 0.9 mmol) and CDI (165 mg, 1 mmol) in 3 mL of dry THF, which had previously been stirred together for 1 h at room temperature, was added. The mixture was allowed to warm to ambient temperature. After 3 days the reaction was quenched with 1 N KH2PO4 and dissolved in ethyl acetate. The organic phase was washed with 1 N KH2PO4, 1 N NaHCO3 (2×) and brine, dried over Na2SO4, and concentrated. Chromatography over silica gel, eluting with 4% to 10% methanol (containing 1% NH4OH) in dichloromethane afforded 124 mg (0.21 mmol) of N1-{(1S,2R)-1-(cyclohexylmethyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N3,N3-dipropylisophthalamide hydrochloride (EXAMPLE SP-256) as a white solid after formation of the salt with ethereal HCl: CI MS m/z 550 [M+H]+. the solvent was removed in vacuo the residue was dissolved in ethyl acetate It was washed three times with small portions of 10% HCl the aqueous phases were back-extracted with ethyl acetate The combined organic phases were washed with 1 N NaHCO3 and brine dried over Na2SO4 concentrated The resulting oil (300 mg) was dissolved in 2 mL of dichloromethane It was concentrated had previously been stirred together for 1 h at room temperature was added to warm to ambient temperature After 3 days the reaction was quenched with 1 N KH2PO4 dissolved in ethyl acetate The organic phase was washed with 1 N KH2PO4, 1 N NaHCO3 (2×) and brine dried over Na2SO4 concentrated Chromatography over silica gel, eluting with 4% to 10% methanol (containing 1% NH4OH) in dichloromethane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: [2-(3-Benzyloxy-5-fluoro-phenyl)-1-oxiranyl-ethyl]-carbamic acid tert-butyl ester (3.33 g, 8.59 mmol) and m-ethyl benzylamine (2.32 g, 17.19 mmol) were dissolved in isopropyl alcohol (80 ml) and brought to reflux for 2 h. Reaction mixture was then concentrated in vacuo to remove isopropyl alcohol. Dissolved yellow liquid in ethyl acetate (30 ml), then washed with 1N HCl (3×100 ml). Aqueous layers were combined then extracted with ethyl acetate (2×100 ml). Organic layers were washed with 10% sodium bicarbonate (aq., 3×100 ml), followed by a brine wash. Organic layer was dried over sodium sulfate, filtered, then concentrated in vacuo, yielding the product (4.31 g). (ES+: 523.9) to reflux for 2 h Reaction mixture was then concentrated in vacuo to remove isopropyl alcohol Dissolved yellow liquid in ethyl acetate (30 ml) washed with 1N HCl (3×100 ml) Aqueous layers were combined then extracted with ethyl acetate (2×100 ml) Organic layers were washed with 10% sodium bicarbonate (aq., 3×100 ml) wash Organic layer was dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: tert-Butyl (1S)-2-(cyclohexyl)-1-[(2S)-oxiran-2-yl]ethylcarbamate (225 mg, 0.84 mmol) was refluxed with m-ethyl benzylamine (254 mg, 1.9 mmol) in 5 mL of isopropanol under nitrogen for 1.5 h, the solvent was removed in vacuo, and the residue was dissolved in ethyl acetate. It was washed three times with small portions of 10% HCl, and the aqueous phases were back-extracted with ethyl acetate. The combined organic phases were washed with 1 N NaHCO3 and brine, dried over Na2SO4, and concentrated. The resulting oil (300 mg) was dissolved in 2 mL of dichloromethane and 2 mL of TFA and stirred for 30 min. It was concentrated, and by weight determined to contain 4 eq. of TFA. This was dissolved in 2 mL of dry THF, and 0.4 mL (3.6 mmol) of 4-methyl morpholine was added. This was cooled to −30° C., and a mixture of 3-[(dipropylamino)carbonyl]-5-methylbenzoic acid (238 mg, 0.9 mmol) and CDI (165 mg, 1 mmol) in 3 mL of dry THF, which had previously been stirred together for 1 h at room temperature, was added. The mixture was allowed to warm to ambient temperature. After 3 days the reaction was quenched with 1 N KH2PO4 and dissolved in ethyl acetate. The organic phase was washed with 1 N KH2PO4, 1 N NaHCO3 (2×) and brine, dried over Na2SO4, and concentrated. Chromatography over silica gel, eluting with 4% to 10% methanol (containing 1% NH4OH) in dichloromethane afforded 124 mg (0.21 mmol) of N1-{(1S,2R)-1-(cyclohexylmethyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N3,N3-dipropylisophthalamide hydrochloride (EXAMPLE SP-256) as a white solid after formation of the salt with ethereal HCl: CI MS m/z 550 [M+H]+. the solvent was removed in vacuo the residue was dissolved in ethyl acetate It was washed three times with small portions of 10% HCl the aqueous phases were back-extracted with ethyl acetate The combined organic phases were washed with 1 N NaHCO3 and brine dried over Na2SO4 concentrated The resulting oil (300 mg) was dissolved in 2 mL of dichloromethane It was concentrated had previously been stirred together for 1 h at room temperature was added to warm to ambient temperature After 3 days the reaction was quenched with 1 N KH2PO4 dissolved in ethyl acetate The organic phase was washed with 1 N KH2PO4, 1 N NaHCO3 (2×) and brine dried over Na2SO4 concentrated Chromatography over silica gel, eluting with 4% to 10% methanol (containing 1% NH4OH) in dichloromethane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: [2-(3-Benzyloxy-5-fluoro-phenyl)-1-oxiranyl-ethyl]-carbamic acid tert-butyl ester (3.33 g, 8.59 mmol) and m-ethyl benzylamine (2.32 g, 17.19 mmol) were dissolved in isopropyl alcohol (80 ml) and brought to reflux for 2 h. Reaction mixture was then concentrated in vacuo to remove isopropyl alcohol. Dissolved yellow liquid in ethyl acetate (30 ml), then washed with 1N HCl (3×100 ml). Aqueous layers were combined then extracted with ethyl acetate (2×100 ml). Organic layers were washed with 10% sodium bicarbonate (aq., 3×100 ml), followed by a brine wash. Organic layer was dried over sodium sulfate, filtered, then concentrated in vacuo, yielding the product (4.31 g). (ES+: 523.9) to reflux for 2 h Reaction mixture was then concentrated in vacuo to remove isopropyl alcohol Dissolved yellow liquid in ethyl acetate (30 ml) washed with 1N HCl (3×100 ml) Aqueous layers were combined then extracted with ethyl acetate (2×100 ml) Organic layers were washed with 10% sodium bicarbonate (aq., 3×100 ml) wash Organic layer was dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: tert-Butyl (1S)-2-(cyclohexyl)-1-[(2S)-oxiran-2-yl]ethylcarbamate (225 mg, 0.84 mmol) was refluxed with m-ethyl benzylamine (254 mg, 1.9 mmol) in 5 mL of isopropanol under nitrogen for 1.5 h, the solvent was removed in vacuo, and the residue was dissolved in ethyl acetate. It was washed three times with small portions of 10% HCl, and the aqueous phases were back-extracted with ethyl acetate. The combined organic phases were washed with 1 N NaHCO3 and brine, dried over Na2SO4, and concentrated. The resulting oil (300 mg) was dissolved in 2 mL of dichloromethane and 2 mL of TFA and stirred for 30 min. It was concentrated, and by weight determined to contain 4 eq. of TFA. This was dissolved in 2 mL of dry THF, and 0.4 mL (3.6 mmol) of 4-methyl morpholine was added. This was cooled to −30° C., and a mixture of 3-[(dipropylamino)carbonyl]-5-methylbenzoic acid (238 mg, 0.9 mmol) and CDI (165 mg, 1 mmol) in 3 mL of dry THF, which had previously been stirred together for 1 h at room temperature, was added. The mixture was allowed to warm to ambient temperature. After 3 days the reaction was quenched with 1 N KH2PO4 and dissolved in ethyl acetate. The organic phase was washed with 1 N KH2PO4, 1 N NaHCO3 (2×) and brine, dried over Na2SO4, and concentrated. Chromatography over silica gel, eluting with 4% to 10% methanol (containing 1% NH4OH) in dichloromethane afforded 124 mg (0.21 mmol) of N1-{(1S,2R)-1-(cyclohexylmethyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N3,N3-dipropylisophthalamide hydrochloride (EXAMPLE SP-256) as a white solid after formation of the salt with ethereal HCl: CI MS m/z 550 [M+H]+. the solvent was removed in vacuo the residue was dissolved in ethyl acetate It was washed three times with small portions of 10% HCl the aqueous phases were back-extracted with ethyl acetate The combined organic phases were washed with 1 N NaHCO3 and brine dried over Na2SO4 concentrated The resulting oil (300 mg) was dissolved in 2 mL of dichloromethane It was concentrated had previously been stirred together for 1 h at room temperature was added to warm to ambient temperature After 3 days the reaction was quenched with 1 N KH2PO4 dissolved in ethyl acetate The organic phase was washed with 1 N KH2PO4, 1 N NaHCO3 (2×) and brine dried over Na2SO4 concentrated Chromatography over silica gel, eluting with 4% to 10% methanol (containing 1% NH4OH) in dichloromethane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: [2-(3-Benzyloxy-5-fluoro-phenyl)-1-oxiranyl-ethyl]-carbamic acid tert-butyl ester (3.33 g, 8.59 mmol) and m-ethyl benzylamine (2.32 g, 17.19 mmol) were dissolved in isopropyl alcohol (80 ml) and brought to reflux for 2 h. Reaction mixture was then concentrated in vacuo to remove isopropyl alcohol. Dissolved yellow liquid in ethyl acetate (30 ml), then washed with 1N HCl (3×100 ml). Aqueous layers were combined then extracted with ethyl acetate (2×100 ml). Organic layers were washed with 10% sodium bicarbonate (aq., 3×100 ml), followed by a brine wash. Organic layer was dried over sodium sulfate, filtered, then concentrated in vacuo, yielding the product (4.31 g). (ES+: 523.9) to reflux for 2 h Reaction mixture was then concentrated in vacuo to remove isopropyl alcohol Dissolved yellow liquid in ethyl acetate (30 ml) washed with 1N HCl (3×100 ml) Aqueous layers were combined then extracted with ethyl acetate (2×100 ml) Organic layers were washed with 10% sodium bicarbonate (aq., 3×100 ml) wash Organic layer was dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: tert-Butyl (1S)-2-(cyclohexyl)-1-[(2S)-oxiran-2-yl]ethylcarbamate (225 mg, 0.84 mmol) was refluxed with m-ethyl benzylamine (254 mg, 1.9 mmol) in 5 mL of isopropanol under nitrogen for 1.5 h, the solvent was removed in vacuo, and the residue was dissolved in ethyl acetate. It was washed three times with small portions of 10% HCl, and the aqueous phases were back-extracted with ethyl acetate. The combined organic phases were washed with 1 N NaHCO3 and brine, dried over Na2SO4, and concentrated. The resulting oil (300 mg) was dissolved in 2 mL of dichloromethane and 2 mL of TFA and stirred for 30 min. It was concentrated, and by weight determined to contain 4 eq. of TFA. This was dissolved in 2 mL of dry THF, and 0.4 mL (3.6 mmol) of 4-methyl morpholine was added. This was cooled to −30° C., and a mixture of 3-[(dipropylamino)carbonyl]-5-methylbenzoic acid (238 mg, 0.9 mmol) and CDI (165 mg, 1 mmol) in 3 mL of dry THF, which had previously been stirred together for 1 h at room temperature, was added. The mixture was allowed to warm to ambient temperature. After 3 days the reaction was quenched with 1 N KH2PO4 and dissolved in ethyl acetate. The organic phase was washed with 1 N KH2PO4, 1 N NaHCO3 (2×) and brine, dried over Na2SO4, and concentrated. Chromatography over silica gel, eluting with 4% to 10% methanol (containing 1% NH4OH) in dichloromethane afforded 124 mg (0.21 mmol) of N1-{(1S,2R)-1-(cyclohexylmethyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methyl-N3,N3-dipropylisophthalamide hydrochloride (EXAMPLE SP-256) as a white solid after formation of the salt with ethereal HCl: CI MS m/z 550 [M+H]+. the solvent was removed in vacuo the residue was dissolved in ethyl acetate It was washed three times with small portions of 10% HCl the aqueous phases were back-extracted with ethyl acetate The combined organic phases were washed with 1 N NaHCO3 and brine dried over Na2SO4 concentrated The resulting oil (300 mg) was dissolved in 2 mL of dichloromethane It was concentrated had previously been stirred together for 1 h at room temperature was added to warm to ambient temperature After 3 days the reaction was quenched with 1 N KH2PO4 dissolved in ethyl acetate The organic phase was washed with 1 N KH2PO4, 1 N NaHCO3 (2×) and brine dried over Na2SO4 concentrated Chromatography over silica gel, eluting with 4% to 10% methanol (containing 1% NH4OH) in dichloromethane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: [2-(3-Benzyloxy-5-fluoro-phenyl)-1-oxiranyl-ethyl]-carbamic acid tert-butyl ester (3.33 g, 8.59 mmol) and m-ethyl benzylamine (2.32 g, 17.19 mmol) were dissolved in isopropyl alcohol (80 ml) and brought to reflux for 2 h. Reaction mixture was then concentrated in vacuo to remove isopropyl alcohol. Dissolved yellow liquid in ethyl acetate (30 ml), then washed with 1N HCl (3×100 ml). Aqueous layers were combined then extracted with ethyl acetate (2×100 ml). Organic layers were washed with 10% sodium bicarbonate (aq., 3×100 ml), followed by a brine wash. Organic layer was dried over sodium sulfate, filtered, then concentrated in vacuo, yielding the product (4.31 g). (ES+: 523.9) to reflux for 2 h Reaction mixture was then concentrated in vacuo to remove isopropyl alcohol Dissolved yellow liquid in ethyl acetate (30 ml) washed with 1N HCl (3×100 ml) Aqueous layers were combined then extracted with ethyl acetate (2×100 ml) Organic layers were washed with 10% sodium bicarbonate (aq., 3×100 ml) wash Organic layer was dried over sodium sulfate filtered concentrated in vacuo