(S)-(+)-2-甲氧基-苯乙胺

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (S)-2-Methoxy-1-phenylethanamine (5.6 g, 37.0 mmol) and potassium cyanate (8.12 g, 100 mmol) were taken up in HCl (1 N, 40 mL, 40.0 mmol) and water (40 mL). The reaction mixture was heated to 100° C. for 3 h. Room temperature was attained, water was added, and the products extracted into EtOAc (×3) followed by 10% MeOH-DCM (×2). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was triturated in Et2O to give (S)-1-(2-methoxy-1-phenylethyl)urea. MS ESI calc'd. for C10H14N2O2 [M+1]+ 195. found 195. Room temperature the products extracted into EtOAc (×3) The combined organic extracts were washed with brine dried over Na2SO4 filtered concentrated in vacuo The residue was triturated in Et2O

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (S)-2-Methoxy-1-phenylethanamine (5.6 g, 37.0 mmol) and potassium cyanate (8.12 g, 100 mmol) were taken up in HCl (1 N, 40 mL, 40.0 mmol) and water (40 mL). The reaction mixture was heated to 100° C. for 3 h. Room temperature was attained, water was added, and the products extracted into EtOAc (×3) followed by 10% MeOH-DCM (×2). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was triturated with Et2O to give (S)-1-(2-methoxy-1-phenylethyl)urea. MS ESI calc'd. for C10H14N2O2 [M+1]+ 195. found 195. Room temperature the products extracted into EtOAc (×3) The combined organic extracts were washed with brine dried over Na2SO4 filtered concentrated in vacuo The residue was triturated with Et2O

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (S)-2-Methoxy-1-phenylethanamine (5.6 g, 37.0 mmol) and potassium cyanate (8.12 g, 100 mmol) were taken up in HCl (1 N, 40 mL, 40.0 mmol) and water (40 mL). The reaction mixture was heated to 100° C. for 3 h. Room temperature was attained, water was added, and the products extracted into EtOAc (×3) followed by 10% MeOH-DCM (×2). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was triturated with Et2O to give (S)-1-(2-methoxy-1-phenylethyl)urea. MS ESI calc'd. for C10H14N2O2 [M+1]+ 195. found 195. Room temperature the products extracted into EtOAc (×3) The combined organic extracts were washed with brine dried over Na2SO4 filtered concentrated in vacuo The residue was triturated with Et2O

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

实验步骤: According to the procedure of Preparation 19 d), tert-butyl (3R)-3-({[(1S)-2,2-dimethyl-1-(carboxy)propyl]amino}carbonyl)-6-(3′-methoxy-2-methylbiphen-4-yl)hexanoate (660 mg, 1.26 mmol) was reacted with (1S)-2-methoxy-1-phenylethylamine (190 mg, 1.260 mmol). Work-up as above, followed by flash chromatography (eluting with hexane:ethyl acetate=3:1) to give tert-butyl (3R)-3-({[(1S)-2,2-dimethyl-1-({[(1s)-2-methoxy-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)-6-(3′-methoxy-2-methylbiphen-4-yl)hexanoate (672 mg, 81%) as a colourless foam. followed by flash chromatography (eluting with hexane:ethyl acetate=3:1)

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

实验步骤: According to the method of Example 25(a), (2R)-N-[(1S)1-(carboxy)-2,2-dimethylpropyl]-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-5-[(3′-methoxy-2-methylbiphen-4-yl)propyl]pentanamide (Preparation 34)(220 mg, 0.42 mmol) was reacted with (1S)-2-methoxy-1-phenylethylamine (63 mg, 0.42 mmol) at room temperature for 2.5 h. The mixture was poured into ethyl acetate (75 mL) and washed with 0.5M aqueous sodium dihydrogenphosphate (2×50 mL) and 5% aqueous sodium bicarbonate (50 mL)(solid sodium chloride was added to give phase separation). The organic solution was dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by flash chromatography (gradient elution with hexane:ethyl acetate=30:70 to 60:40) to give a white solid which was purified again by flash chromatography (sorbsil C60, (20-40μ) silica gel, eluting with hexane:ethyl acetate 35:65) to give (2R)-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-N-[(1S)-2,2-dimethyl-1-({[(1S)-2-methoxy-1-phenylethyl]amino}carbonyl)propyl]-5-[(3′-methoxy-2-methylbiphen-4-yl)propyl]pentanamide as a white solid (191 mg, 69%). washed with 0.5M aqueous sodium dihydrogenphosphate (2×50 mL) and 5% aqueous sodium bicarbonate (50 mL)(solid sodium chloride was added to give phase separation) The organic solution was dried (Na2SO4) concentrated under reduced pressure The residue was purified by flash chromatography (gradient elution with hexane:ethyl acetate=30:70 to 60:40) to give a white solid which was purified again by flash chromatography (sorbsil C60, (20-40μ) silica gel, eluting with hexane:ethyl acetate 35:65)

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (S)-2-Methoxy-1-phenylethanamine (5.6 g, 37.0 mmol) and potassium cyanate (8.12 g, 100 mmol) were taken up in HCl (1 N, 40 mL, 40.0 mmol) and water (40 mL). The reaction mixture was heated to 100° C. for 3 h. Room temperature was attained, water was added, and the products extracted into EtOAc (×3) followed by 10% MeOH-DCM (×2). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was triturated in Et2O to give (S)-1-(2-methoxy-1-phenylethyl)urea. MS ESI calc'd. for C10H14N2O2 [M+1]+ 195. found 195. Room temperature the products extracted into EtOAc (×3) The combined organic extracts were washed with brine dried over Na2SO4 filtered concentrated in vacuo The residue was triturated in Et2O

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (S)-2-Methoxy-1-phenylethanamine (5.6 g, 37.0 mmol) and potassium cyanate (8.12 g, 100 mmol) were taken up in HCl (1 N, 40 mL, 40.0 mmol) and water (40 mL). The reaction mixture was heated to 100° C. for 3 h. Room temperature was attained, water was added, and the products extracted into EtOAc (×3) followed by 10% MeOH-DCM (×2). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was triturated with Et2O to give (S)-1-(2-methoxy-1-phenylethyl)urea. MS ESI calc'd. for C10H14N2O2 [M+1]+ 195. found 195. Room temperature the products extracted into EtOAc (×3) The combined organic extracts were washed with brine dried over Na2SO4 filtered concentrated in vacuo The residue was triturated with Et2O