methyl 2-[[(1S)-1-phenylethyl]amino]acetate

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

Procedure: To a solution of (S)-α-methylbenzylamine (3.87 mL, 0.03 mol) in acetonitrile (50 mL) was added diisopropylethylamine (5.23 mL, 0.03 mol), followed by methyl bromoacetate (2.84 mL, 0.03 mol). The reaction was stirred under nitrogen, at room temperature, overnight. The solution was concentrated and the residue partitioned between ethyl acetate and saturated NaHCO3. The aqueous layer was separated, and the product extracted three times with ethyl acetate. The ethyl acetate solutions were combined, washed three times with brine, dried over MgSO4, and concentrated to give a light yellow liquid. Chromatography was carried out on silica gel, using ethyl acetate as eluent, to give a colorless liquid; 4.97 g (86% yield). MS-APCI: M+1=194.2. The solution was concentrated the residue partitioned between ethyl acetate and saturated NaHCO3 The aqueous layer was separated the product extracted three times with ethyl acetate washed three times with brine dried over MgSO4 concentrated to give a light yellow liquid to give a colorless liquid

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

Procedure: Scheme 1 shows a method by which the compounds of the present invention can be prepared, by illustrating the synthesis of Example 1, benzyl N-((1S)-1-(1H-4-imidazolylmethyl)-2-2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl[(1S)-1-phenylethyl]amino-2-oxoethyl)carbamate. Reaction of (S)-α-methylbenzylamine with methyl bromoacetate was carried out in acetonitrile in the presence of dilsopropylethylamine as the base to give methyl-2-[(1S)-1-phenylethyl]aminoacetate. Methyl-2-[(1S)-1-phenylethyl]aminoacetate was then coupled to Cbz-His(trityl) in methylene chloride with HATU as coupling agent, and diisopropylethylamine as the base. The resulting product was saponified using lithium hydroxide at 0° C., followed by coupling with β,β-dimethylphenethylamine in methylene chloride, with HBTU as coupling agent, and diisopropylethylamine as the base. The trityl group was removed by treatment with 50% TFA in methylene chloride. The β,β-dimethylphenethylamine was prepared from benzyl cyanide, which was treated with 2 equivalents of sodium hydride in tetrahydrofuran (THF) and 2 equivalents of methyl iodide in THF followed by hydrogenation (H2, Pd/C, ammonia) and treatment with HCl to give the HCl salt. can be prepared

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

Procedure: To a solution of (S)-α-methylbenzylamine (3.87 mL, 0.03 mol) in acetonitrile (50 mL) was added diisopropylethylamine (5.23 mL, 0.03 mol), followed by methyl bromoacetate (2.84 mL, 0.03 mol). The reaction was stirred under nitrogen, at room temperature, overnight. The solution was concentrated and the residue partitioned between ethyl acetate and saturated NaHCO3. The aqueous layer was separated, and the product extracted three times with ethyl acetate. The ethyl acetate solutions were combined, washed three times with brine, dried over MgSO4, and concentrated to give a light yellow liquid. Chromatography was carried out on silica gel, using ethyl acetate as eluent, to give a colorless liquid; 4.97 g (86% yield). MS-APCI: M+1=194.2. The solution was concentrated the residue partitioned between ethyl acetate and saturated NaHCO3 The aqueous layer was separated the product extracted three times with ethyl acetate washed three times with brine dried over MgSO4 concentrated to give a light yellow liquid to give a colorless liquid

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

Procedure: Scheme 1 shows a method by which the compounds of the present invention can be prepared, by illustrating the synthesis of Example 1, benzyl N-((1S)-1-(1H-4-imidazolylmethyl)-2-2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl[(1S)-1-phenylethyl]amino-2-oxoethyl)carbamate. Reaction of (S)-α-methylbenzylamine with methyl bromoacetate was carried out in acetonitrile in the presence of dilsopropylethylamine as the base to give methyl-2-[(1S)-1-phenylethyl]aminoacetate. Methyl-2-[(1S)-1-phenylethyl]aminoacetate was then coupled to Cbz-His(trityl) in methylene chloride with HATU as coupling agent, and diisopropylethylamine as the base. The resulting product was saponified using lithium hydroxide at 0° C., followed by coupling with β,β-dimethylphenethylamine in methylene chloride, with HBTU as coupling agent, and diisopropylethylamine as the base. The trityl group was removed by treatment with 50% TFA in methylene chloride. The β,β-dimethylphenethylamine was prepared from benzyl cyanide, which was treated with 2 equivalents of sodium hydride in tetrahydrofuran (THF) and 2 equivalents of methyl iodide in THF followed by hydrogenation (H2, Pd/C, ammonia) and treatment with HCl to give the HCl salt. can be prepared