Name: 53934-78-4|(S)-tert-Butyl 2-amino-2-phenylacetate|97%
Brand: Ambeed
SKU: A184155
Price: 6.0 USD
Availability: InStock
Rating: 98 (22 reviews)

1
[ 53934-78-4 ]
[ 72087-11-7 ]
[ 76314-24-4 ]
[ 73537-60-7 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1980,vol. 53,p. 283 - 284

2
[ 5891-45-2 ]
[ 53934-78-4 ]
[ 161878-65-5 ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 3294 - 3302

3
[ 875-74-1 ]
[ 115-11-7 ]
[ 53934-78-4 ]

Reference： [1]Journal of the American Chemical Society,1995,vol. 117,p. 10879 - 10888

4
[ 53934-78-4 ]
[ 2043-61-0 ]
(R)-[1-Cyclohexyl-meth-(E)-ylidene]-amino}-phenyl-acetic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1995,vol. 117,p. 10879 - 10888

5
[ 53934-78-4 ]
[ 407-25-0 ]
(R)-Phenyl-(2,2,2-trifluoro-acetylamino)-acetic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1997,p. 247 - 249

6
[ 53934-78-4 ]
[ 79-44-7 ]
[ 1007879-90-4 ]

Yield	Reaction Conditions	Operation in experiment
75%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 3h;	To a stirred solution of (R)-tert-butyl-2~amino-2-phenylacetate (1.0 g, 4.10 mmol) and Hunig's base (1.79 mL, 10.25 mmol) in DMF (40 mL) was added dimethylcarbamoyl chloride (0.38 mL, 4.18 mmol) dropwise over 10 minutes. After stirring at room temperature for 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate. The organic layer was washed with H2O, IN aq. HCl and brine, dried (MgSO4), filtered and concentrated under reduced pressure. (R)-tert~butyl 2-(3,3-dimethylureido)-2-phenylacetate was obtained as a white solid ( 0.86 g; 75%) and used without further purification. 1H. NMR (500 MHz, DMSO-ds) delta ppm 1.33 (s, 9H) 2.82 (s, 6H) 5.17 (d, J-7.63 Hz5 IH) 6.55 (d, /=7.32 Hz, IH) 7.24-7.41 (m, 5H). LCMS: Anal. Calcd. for C15H22N2O3 278.16 found 279.23 (M+H)+; HPLC Phenomenex LUNA C-18 4.6 X 50 mm, 0 to 100% B over 4 minutes, 1 minute hold time, A=90% water, 10% methanol, 0.1% TFA, B=10% water, 90% methanol, 0.1% TFA, RT=2.26 min, 97% homogeneity index.
75%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;	To a stirred solution of (R)-tert-butyI-2-animo-2-phenylacetate ( 1.0 g, 4.10 mmol) and Hunig's base (1.79 mL, 10.25 mmol) in DMF (40 mL) was added dimethylcarbamoyl chloride (0.38 mL, 4.18 mmol) dropwise over 10 minutes. After stirring at room temperature for 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate. The organic layer was washed with H2O, IN aq. HCl and brine, dried (MgSO^, filtered and concentrated under reduced pressure. (R)-fetaut-butyl 2-(3,3-dimethylureido)-2- phenylacetate was obtained as a white solid (0.86 g; 75%) and used without further purification. 1H NMR (500 MHz, DMSOd6) delta ppm 1.33 (s, 9H) 2.82 (s, 6H) 5.17 (d, J=7.63 Hz, IH) 6.55 (d, J=7.32 Hz, IH) 7.24-7.41 (m, 5H). LCMS: Anal. Cacd. for C15H22N2O3 278.16 found 279.23 (M+H)÷; HPLC PHEN0MENEX LUNA C-18 4.6 x 50 mm, 0 to 100% B over 4 minutes, 1 minute hold time, A-90% water, 10% methanol, 0.1% TFA, B=I 0% water, 90% methanol, 0.1% TFA, RT-2.26 mm, 97% homogeneity index.
75%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 3.16667h;	To a stirred solution of <strong>[53934-78-4](R)-tert-butyl-2-amino-2-phenylacetate</strong> (1.0 g, 4.10 mmol) and Hunig's base (1.79 mL, 10.25 mmol) in DMF (40 mL) was added dimethylcarbamoyl chloride (0.38 mL, 4.18 mmol) dropwise over 10 minutes. After stirring at room temperature for 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate. The organic layer was washed with H20, IN aq. HCl and brine, dried (MgS04), filtered and concentrated under reduced pressure. (R)-tert-butyl 2-(3,3-dimethylureido)-2-phenylacetate was obtained as a white solid (0.86 g; 75%) and used without further purification. ¾ NMR (500 MHz, DMSO-d6) delta ppm 1.33 (s, 9H) 2.82 (s, 6H) 5.17 (d, J=7.63 Hz, IH) 6.55 (d, J=7.32 Hz, IH) 7.24-7.41 (m, 5H). LCMS: Anal. Calcd. for C15H22N2O3 278.16 found 279.23 (M+H)+; HPLC PHENOMENEX Luna C- 18 4.6 x 50 mm, 0 to 100% B over 4 minutes, 1 minute hold time, A=90% water, 10% methanol, 0.1% TFA, B=10% water, 90% methanol, 0.1% TFA, RT=2.26 min, 97% homogeneity index.

75%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 3.16667h;	To a stirred solution of <strong>[53934-78-4](R)-tert-butyl-2-amino-2-phenylacetate</strong> (1.0 g, 4.10 mmol) and Hunig's base (1.79 mL, 10.25 mmol) in DMF (40 mL) was added dimethylcarbamoyl chloride (0.38 mL, 4.18 mmol) dropwise over 10 minutes. After stirring at room temperature for 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate. The organic layer was washed with H20, IN aq. HC1 and brine, dried (MgS04), filtered and concentrated under reduced pressure. (R)-tert-butyl 2- (3,3-dimethylureido)-2-phenylacetate was obtained as a white solid (0.86 g; 75%) and used without further purification. 1H NMR (500 MHz, DMSO-d6) delta ppm 1.33 (s, 9H)2.82 (s, 6H) 5.17 (d, J=7.63 Hz, IH) 6.55 (d, J=7.32 Hz, IH) 7.24-7.41 (m, 5H). LCMS: Anal. Calcd. for C15H22N203 278.16 found 279.23 (M+H)+; HPLC PHENOMENEX LUNA C-18 4.6 x 50 mm, 0 to 100% B over 4 minutes, 1 minute hold time, A=90% water, 10% methanol, 0.1% TFA, B=10% water, 90% methanol, 0.1% TFA, RT=2.26 min, 97% homogeneity index.
75%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 3.16667h;	[00176] Step 1 : (R)-tert-Butyl 2-(3,3-dimethylureido)-2-phenylacetate. To a stirred solution of <strong>[53934-78-4](R)-tert-butyl-2-amino-2-phenylacetate</strong> (1.0 g, 4.10 mmol) and Hunig's base (1.79 mL, 10.25 mmol) in DMF (40 mL) was added dimethylcarbamoyl chloride (0.38 mL, 4.18 mmol) dropwise over 10 minutes. After stirring at room temperature for 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate. The organic layer was washed with H20, IN aq. HC1 and brine, dried (MgS04), filtered and concentrated under reduced pressure. (R)-tert-butyl 2- (3,3-dimethylureido)-2-phenylacetate was obtained as a white solid (0.86 g; 75%) and used without further purification. ¾ NMR (500 MHz, DMSO-d6) delta ppm 1.33 (s, 9H) 2.82 (s, 6H) 5.17 (d, J=7.63 Hz, IH) 6.55 (d, J=7.32 Hz, IH) 7.24-7.41 (m, 5H). LC- MS: Anal. Calcd. for Ci5H22N203 278.16 found 279.23 (M+H)+; HPLCPHENOMENEX Luna C- 18 4.6 x 50 mm, 0 to 100% B over 4 minutes, 1 minute hold time, A=90% water, 10% methanol, 0.1% TFA, B=10% water, 90% methanol, 0.1% TFA, RT=2.26 min, 97% homogeneity index.
75%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 3h;	Step 1; (R)-tert-butyl 2-(3,3-dimethylureido)-2-phenylacetate: To a stirred solution of <strong>[53934-78-4](R)-tert-butyl-2-amino-2-phenylacetate</strong> (1.0 g, 4.10 mmol) and Hunig's base (1.79 mL, 10.25 mmol) in DMF (40 mL) was added dimethylcarbamoyl chloride (0.38 mL, 4.18 mmol) dropwise over 10 minutes. After stirring at room temperature for 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate. The organic layer was washed with H20, IN aq. HC1 and brine, dried (MgS04), filtered and concentrated under reduced pressure. (R)-tert-butyl 2-(3,3-dimethylureido)-2-phenylacetate was obtained as a white solid ( 0.86 g; 75%) and used without further purification. XH NMR (500 MHz, DMSO-d6) delta ppm 1.33 (s, 9H) 2.82 (s, 6H) 5.17 (d, J=7.63 Hz, 1H) 6.55 (d, J=7.32 Hz, 1H) 7.24-7.41 (m, 5H). LCMS: Anal. Calcd. for Ci5H22N203 278.16 found 279.23 (M+H)+; HPLC Phenomenex LUNA C-18 4.6 x 50 mm, 0 to 100%) B over 4 minutes, 1 minute hold time, A=90%> water, 10%> methanol, 0.1 %> TFA, B=10% water, 90% methanol, 0.1% TFA, RT=2.26 min, 97% homogeneity index.
75%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 3.16667h;	Step 1; (R)-tert-butyl 2-(3,3-dimethylureido)-2-phenylacetate: To a stirred solution of <strong>[53934-78-4](R)-tert-butyl-2-amino-2-phenylacetate</strong> (1.0 g, 4. 10 mmol) and Hunig's base (1.79 mL, 10.25 mmol) in DMF (40 mL) was added dimethylcarbamoyl chloride (0.38 mL, 4.18 mmol) dropwise over 10 minutes. After stirring at room temperature for 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate. The organic layer was washed with H2O, 1N aq. HCl and brine, dried (MgSO4), filtered and concentrated under reduced pressure. (R)-tert-butyl 2-(3,3-dimethylureido)-2-phenylacetate was obtained as a white solid (0.86 g; 75%) and used without further purification. 1H NMR (500 MHz, DMSO-d6) delta ppm 1.33 (s, 9H) 2.82 (s, 6H) 5.17 (d, J=7.63 Hz, 1H) 6.55 (d, J=7.32 Hz, 1H) 7.24-7.41 (m, 5H). LCMS: Anal. Calcd. for C15H22N2O3 278.16 found 279.23 (M+H)+; HPLC Phenomenex LUNA C-18 4.6*50 mm, 0 to 100% B over 4 minutes, 1 minutes hold time, A=90% water, 10% methanol, 0.1% TFA, B=10% water, 90% methanol, 0.1% TFA, RT=2.26 min, 97% homogeneity index.
75%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 3.16667h;	To a stirred solution of <strong>[53934-78-4](R)-tert-butyl-2-amino-2-phenylacetate</strong> (1.0 g, 4. 10 mmol) and Hunig's base (1.79 mL, 10.25 mmol) in DMF (40 mL) was added dimethylcarbamoyl chloride (0.38 mL, 4.18 mmol) dropwise over 10 minutes. After stirring at room temperature for 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate. The organic layer was washed with H2O, 1N aq. HCl and brine, dried (MgSO4), filtered and concentrated under reduced pressure. (R)-tert-butyl 2-(3,3-dimethylureido)-2-phenylacetate was obtained as a white solid ( 0.86 g; 75%) and used without further purification. 1H NMR (500 MHz, DMSO-d6) delta ppm 1.33 (s, 9H) 2.82 (s, 6H) 5.17 (d, J=7.63 Hz, 1H) 6.55 (d, J=7.32 Hz, 1H) 7.24-7.41 (m, 5H). LCMS: Anal. Calcd. for C15H22N2O3 278.16 found 279.23 (M+H)+; HPLC Phenomenex LUNA C-18 4.6×50 mm, 0 to 100% B over 4 minutes, 1 minutes hold time, A=90% water, 10% methanol, 0.1% TFA, B=10% water, 90% methanol, 0.1% TFA, RT=2.26 min, 97% homogeneity index.
75%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 3.16667h;	To a stirred solution of <strong>[53934-78-4](R)-tert-butyl-2-amino-2-phenylacetate</strong> (1.0 g, 4.10 mmol) and Hunig's base (1.79 mL, 10.25 mmol) in DMF (40 mL) was added dimethylcarbamoyl chloride (0.38 mL, 4.18 mmol) dropwise over 10 minutes. After stirring at room temperature for 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate. The organic layer was washed with H2O, IN aq. HCl and brine, dried (MgSO4), filtered and concentrated under reduced pressure. (R)-tert-butyl 2-(3,3-dimethylureido)-2-phenylacetate was obtained as a white solid ( 0.86 g; 75%) and used without further purification. 1H NMR (500 MHz, DMSO-d6) delta ppm 1.33 (s, 9H) 2.82 (s, 6H) 5.17 (d, J=7.63 Hz, IH) 6.55 (d, J=7.32 Hz, IH) 7.24-7.41 (m, 5H). LCMS: Anal. Calcd. for Ci5H22N2O3 278.16 found 279.23 (M+H)+; HPLC Phenomenex LUNA C-18 4.6 x 50 mm, 0 to 100% B over 4 minutes, 1 minute hold time, A=90% water, 10% methanol, 0.1% TFA, B= 10% water, 90% methanol, 0.1% TFA, RT=2.26 min, 97% homogeneity index.
75%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 3.16667h;	Step 1; (R)-tert-butyl 2-(3,3-dimethylureido)-2-phenylacetate: To a stirred solution of <strong>[53934-78-4](R)-tert-butyl-2-amino-2-phenylacetate</strong> (1.0 g, 4.10 mmol) and Hunig's <n="71"/>base (1.79 mL, 10.25 mmol) in DMF (40 mL) was added dimethylcarbamoyl chloride (0.38 mL, 4.18 mmol) dropwise over 10 minutes. After stirring at room temperature for 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate. The organic layer was washed with H2O, IN aq. HCl and brine, dried (MgSO4), filtered and concentrated under reduced pressure. (R)-tert-butyl 2-(3,3-dimethylureido)-2-phenylacetate was obtained as a white solid ( 0.86 g; 75%) and used without further purification. 1H NMR (500 MHz, DMSO-d6) delta ppm 1.33 (s, 9H) 2.82 (s, 6H) 5.17 (d, J=7.63 Hz, IH) 6.55 (d, J=7.32 Hz, IH) 7.24 - 7.41 (m, 5H). LCMS: Anal. Calcd. for Ci5H22N2O3 278.16 found 279.23 (M+H)+; HPLC Phenomenex LUNA C-18 4.6 x 50 mm, 0 to 100% B over 4 minutes, 1 minutes hold time, A = 90% water, 10% methanol, 0.1% TFA, B = 10% water, 90% methanol, 0.1% TFA, RT = 2.26 min, 97% homogeneity index.
75%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;	Step 1; (R)-tert-butyl 2-(3,3-dimethylureido)-2-phenylacetate: To a stirred solution of <strong>[53934-78-4](R)-tert-butyl-2-amino-2-phenylacetate</strong> (1.0 g, 4.10 mmol) and Hunig's base (1.79 mL, 10.25 mmol) in DMF (40 mL) was added dimethylcarbamoyl chloride (0.38 mL, 4.18 mmol) dropwise over 10 minutes. After stirring at room temperature for 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate. The organic layer was washed with H2O, 1N aq. HCl and brine, dried (MgSO4), filtered and concentrated under reduced pressure. (R)-tert-butyl 2-(3,3-dimethylureido)-2-phenylacetate was obtained as a white solid (0.86 g; 75%) and used without further purification. 1H NMR (500 MHz, DMSO-d6) delta ppm 1.33 (s, 9H) 2.82 (s, 6H) 5.17 (d, J=7.63 Hz, 1H) 6.55 (d, J=7.32 Hz, 1H) 7.24-7.41 (m, 5H). LCMS: Anal. Calcd. for C15H22N2O3 278.16 found 279.23 (M+H)+; HPLC Phenomenex LUNA C-18 4.6×50 mm, 0 to 100% B over 4 minutes, 1 minute hold time, A=90% water, 10% methanol, 0.1% TFA, B=10% water, 90% methanol, 0.1% TFA, RT=2.26 min, 97% homogeneity index.
71%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 3h;	To a stirred solution of <strong>[53934-78-4](R)-tert-butyl-2-amino-2-phenylacetate</strong> (1.0 g, 4.10 mmol) and Hunig?s base (1.79 mL, 10.25 mmol) in DMF (40 mL) was added dimethylcarbamoyl chloride (0.38 mL, 4.18 mmol) dropwise over 10 minutes. After stirring at room temperature for 3 hours, the reactionwas concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate. The organic layerwas washed with H2O, 1N aq. HCl and brine, dried (MgSO4, filtered and concentrated under reduced pressure. (R)-tertbutyl2-(3,3-dimethylureido)-2-phenylacetate was obtained as a white solid (0.86 g; 75%) and used without furtherpurification. 1H NMR (500 MHz, DMSO-d6) delta ppm 1.33 (s, 9H) 2.82 (s, 6H) 5.17 (d, J=7.63 Hz, 1H) 6.55 (d, J=7.32 Hz,1H) 7.24-7.41 (m, 5H). LCMS: Anal. Calcd. for C15H22N2O3 278.16 found 279.23 (M+H)+; HPLC Phenomenex LUNAC-18 4.6 3 50 mm, 0 to 100% B over 4 minutes, 1 minute hold time, A=90% water, 10% methanol, 0.1 % TFA, B=10%water, 90% methanol, 0.1% TFA, RT=2.26 min, 97% homogeneity index.
	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 3.16667h;	To a stirred solution of <strong>[53934-78-4](R)-tert-butyl-2-amino-2-phenylacetate</strong> (1.0 g, 4.10 mmol) and Hunig's base (1.79 mL, 10.25 mmol) in DMF (40 mL) was added dimethylcarbamoyl chloride (0.38 mL, 4.18 mmol) dropwise over 10 minutes. After stirring at room temperature for 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate. The organic layer was washed with H2O, 1N aq. HCl and brine, dried (MgSO4), filtered and concentrated under reduced pressure. (R)-tert-butyl 2-(3,3-dimethylureido)-2-phenylacetate was obtained as a white solid (0.86 g; 75%) and used without further purification. 1H NMR (500 MHz, DMSO-d6) delta ppm 1.33 (s, 9H) 2.82 (s, 6H) 5.17 (d, J=7.63 Hz, 1H) 6.55 (d, J=7.32 Hz, 1H) 7.24-7.41 (m, 5H). LCMS: Anal. Calcd. for C15H22N2O3 278.16 found 279.23 (M+H)+; HPLC Phenomenex LUNA C-18 4.6×50 mm, 0 to 100% B over 4 minutes, 1 minute hold time, A=90% water, 10% methanol, 0.1% TFA, B=10% water, 90% methanol, 0.1% TFA, RT=2.26 min, 97% homogeneity index.
	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 3.16667h;	To a stirred solution of (R) -tert-butyl - 2-amino-2-phenylacetate (1.0 g, 4.10 mtnol) and Hunig's base (1.79 mL, 10.25 mmol) in DMF (40 mL) was added dimethylcarbamoyl chloride (0.38 mL, 4.18 mmol) dropwise over 10 minutes. After stirring at room temperature for115 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate. The organic layer was washed with H2O, IN aq. HCl and brine, dried (MgSO4) , filtered and concentrated under reduced pressure. (R) -tert-hutyl 2- (3,3- dimethylureido) -2-phenylacetate was obtained as a white solid ( 0.86 g; 75%) and used without further purification. 1H NMR (500 MHz, DMS0-d6) delta ppm 1.33 (s, 9H) 2.82 (s, 6H) 5.17 (d, J=7.63 Hz, IH) 6.55 (d, J=7.32 Hz, IH) 7.24-7.41 (m, 5H) . LCMS: Anal. Calcd. forC15H22N2O3 278.16 found 279.23 (M+H)+; HPLC Phenomenex LUWA C- 18 4.6 X 50 mm, 0 to 100% B over 4 minutes, 1 minute hold time, A=90% water, 10% methanol, 0.1% TFA, B=10% water, 90% methanol, 0.1% TFA, RT=2.26 mi?, 97% homogeneity index.
	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 3h;	To a stirred solution of (R)-tert-butyl-2-amino-2-rhohenylacetate (1.0 g, 4.10 mmol) and Hunig's base (1.79 niL, 10.25 mmol) in DMF (40 mL) was added dimethylcarbamoyl chloride (0.38 mL, 4.18 mmol) dropwise over 10 minutes. After stirring at room temperature for 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate. The organic layer was washed with H2O, IN aq. HCl and brine, dried (MgSO^, filtered and concentrated under reduced pressure. (R)-tert-buty 2-(3,3-dimethylureido)-2- phenylacetate was obtained as a white solid (0.86 g; 75%) and used without further purification. 1H NMR (500 MHz, DMSOd6) delta ppm 1.33 (s, 9H) 2.82 (s, 6H) 5.17 (d, J-7.63 Hz, IH) 6.55 (d, J=7.32 Hz, IH) 7.24-7.41 (m, 5H). LCMS: Anal. Calcd. for C15H22N2O3 278.16 found 279.23 (M+H)÷; HPLC PHENOMENEX LUNA C-18 4.6 x 50 mm, 0 to 100% B over 4 minutes, 1 minute hold time, A=90% water, 10% methanol, 0.1% TFA, B=I 0% water, 90% methanol, 0.1% TFA, RT=2.26 min, 97% homogeneity index.

Reference： [1]Patent: WO2010/17401,2010,A1 .Location in patent: Page/Page column 213
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[4]Patent: WO2011/59850,2011,A1 .Location in patent: Page/Page column 64
[5]Patent: WO2011/75439,2011,A1 .Location in patent: Page/Page column 59
[6]Patent: WO2012/18325,2012,A1 .Location in patent: Page/Page column 62
[7]Patent: US2008/44380,2008,A1 .Location in patent: Page/Page column 47
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[9]Patent: WO2008/144380,2008,A1 .Location in patent: Page/Page column 74
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[11]Patent: US2010/249190,2010,A1 .Location in patent: Page/Page column 40
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[13]Patent: US2009/233925,2009,A1 .Location in patent: Page/Page column 33
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7
[ 4747-71-1 ]
[ 53934-78-4 ]
[ 1007879-96-0 ]

Yield	Reaction Conditions	Operation in experiment
100%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 3h;	To a stirred solution of (R)-2-amino-2-phenylacetic acid hydrochloride (1.0 g, 4.10 mraol) and Hunig's base (1.0 mL, 6.15 mmol) in DMF (15 niL) was added cyclopentyl isocyanate (0.46 mL, 4.10 mmol) dropwise and over 10 minutes. After stirring at room temperature for 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was traken up in ethyl acetate. The organic layer was washed with H2O and brine, dried (MgSO4), filtered, and concentrated under reduced pressure. (R)-tert-butyl 2-(3-cyclopentylureido)-2-phenylacetate was obtained as an opaque oil (1.32 g; 100 %) and used without further purification. 1H NMR (500 MHz, CD3Cl-D) delta ppm 1.50-1.57 (m, 2H) 1.58-1.66 (m, 2H) 1.87-1.97 (m, 2H) 3.89- 3.98 (m, IH) 5.37 (s, IH) 7.26-7.38 (m, 5H). LCMS: Anal. Calcd. J7Or Ci8Ha5N2O3 318.19 found 319.21 (M+H)+; HPLC XTERRA C-18 3.0 x 50 mm, 0 to 100% B over 4 minutes, 1 minute hold time, A=90% water, 10% methanol, 0.1% TFA, B-10% water, 90% methanol, 0.1% TFA, RT=2.82 min, 96% homogeneity index.
100%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 3h;	To a stirred solution of (R)-2-amino-2-phenylaceticacid hydrochloride (1.0 g, 4.10 mmol) and Hunig?s base (1.0 mL, 6.15 mmol) in DMF (15 mL) was added cyclopentylisocyanate (0.46 mL, 4.10 mmol) dropwise and over 10 minutes. After stirring at room temperature for 3 hours, thereaction was concentrated under reduced pressure and the resulting residue was traken up in ethyl acetate. The organiclayer was washed with H2O and brine, dried (MgSO4), filtered, and concentrated under reduced pressure. (R)-tert-butyl2-(3-cyclopentylureido)-2-phenylacetate was obtained as an opaque oil (1.32 g; 100 %) and used without further purification.1H NMR (500 MHz, CD3Cl-D) delta ppm 1.50-1.57 (m, 2H) 1.58-1.66 (m, 2H) 1.87-1.97 (m, 2H) 3.89-3.98 (m, 1H)5.37 (s, 1H) 7.26-7.38 (m, 5H). LCMS: Anal. Calcd. for C18H26N2O3 318.19 found 319.21 (M+H)+; HPLC XTERRA C-18 3.0 x 50 mm, 0 to 100% B over 4 minutes, 1 minute hold time, A=90% water, 10% methanol, 0.1% TFA, B=10%water, 90% methanol, 0.1% TFA, RT=2.82 min, 96% homogeneity index.
100%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 3.16667h;	Step 1; (R)-tert-butyl 2-(3-cyclopentylureido)-2-phenylacetate: To a stirred solution of (R)-2-amino-2-phenylacetic acid hydrochloride (1.0 g, 4.10 mmol) and Hunig's base (1.0 mL, 6.15 mmol) in DMF (15 mL) was added cyclopentyl isocyanate (0.46 mL, 4. 10 mmol) dropwise and over 10 minutes. After stirring at room temperature for 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was traken up in ethyl acetate. The organic layer was washed with H2O and brine, dried (MgSO4), filtered, and concentrated under reduced pressure. (R)-tert-butyl 2-(3-cyclopentylureido)-2-phenylacetate was obtained as an opaque oil (1.32 g; 100%) and used without further purification. 1H NMR (500 MHz, CD3Cl-D) delta ppm 1.50-1.57 (m, 2H) 1.58-1.66 (m, 2H) 1.87-1.97 (m, 2H) 3.89-3.98 (m, 1H) 5.37 (s, 1H) 7.26-7.38 (m, 5H). LCMS: Anal. Calcd. for C18H26N2O3 318.19 found 319.21 (M+H)+; HPLC XTERRA C-18 3.0*50 mm, 0 to 100% B over 4 minutes, 1 minutes hold time, A=90% water, 10% methanol, 0.1% TFA, B=10% water, 90% methanol, 0.1% TFA, RT=2.82 min, 96% homogeneity index.

100%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;	Step 1; (R)-tert-butyl 2-(3-cyclopentylureido)-2-phenylacetate: To a stirred solution of (R)-2-amino-2-phenylacetic acid hydrochloride (1.0 g, 4.10 mmol) and Hunig's base (1.0 mL, 6.15 mmol) in DMF (15 mL) was added cyclopentyl isocyanate (0.46 mL, 4.10 mmol) dropwise and over 10 minutes. After stirring at room temperature for 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was taken up in ethyl acetate. The organic layer was washed with H2O and brine, dried (MgSO4), filtered, and concentrated under reduced pressure. (R)-tert-butyl 2-(3-cyclopentylureido)-2-phenylacetate was obtained as an opaque oil (1.32 g; 100%) and used without further purification. 1H NMR (500 MHz, CD3Cl-D) delta ppm 1.50-1.57 (m, 2H) 1.58-1.66 (m, 2H) 1.87-1.97 (m, 2H) 3.89-3.98 (m, 1H) 5.37 (s, 1H) 7.26-7.38 (m, 5H). LCMS: Anal. Calcd. for C18H26N2O3 318.19 found 319.21 (M+H)+; HPLC XTERRA C-18 3.0×50 mm, 0 to 100% B over 4 minutes, 1 minute hold time, A=90% water, 10% methanol, 0.1% TFA, B=10% water, 90% methanol, 0.1% TFA, RT=2.82 min, 96% homogeneity index.
	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 3.16667h;	To a stirred solution of (R)-2-amino-2-phenylacetic acid hydrochloride (1.0 g, 4.10 mmol) and Hunig's base (1.0 mL, 6.15 mmol) in DMF (15 mL) was added cyclopentyl isocyanate (0.46 mL, 4.10 mmol) dropwise and over 10 minutes. After stirring at room temperature for 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was taken up in ethyl acetate. The organic layer was washed with H2O and brine, dried (MgSO4), filtered, and concentrated under reduced pressure. (R)-tert-butyl 2-(3-cyclopentylureido)-2-phenylacetate was obtained as an opaque oil (1.32 g; 100%) and used without further purification. 1H NMR (500 MHz, CD3Cl-D) delta ppm 1.50-1.57 (m, 2H) 1.58-1.66 (m, 2H) 1.87-1.97 (m, 2H) 3.89-3.98 (m, 1H) 5.37 (s, 1H) 7.26-7.38 (m, 5H). LCMS: Anal. Calcd. for C18H26N2O3 318.19 found 319.21 (M+H)+; HPLC XTERRA C-18 3.0×50 mm, 0 to 100% B over 4 minutes, 1 minute hold time, A=90% water, 10% methanol, 0.1% TFA, B=10% water, 90% methanol, 0.1% TFA, RT=2.82 min, 96% homogeneity index.

Reference： [1]Patent: WO2010/17401,2010,A1 .Location in patent: Page/Page column 214
[2]Patent: EP2328865,2017,B1 .Location in patent: Paragraph 0408-0409
[3]Patent: US2008/44380,2008,A1 .Location in patent: Page/Page column 47
[4]Patent: US2010/249190,2010,A1 .Location in patent: Page/Page column 41
[5]Patent: US2009/233925,2009,A1 .Location in patent: Page/Page column 33-34

8
[ 53934-78-4 ]
[ 111-30-8 ]
[ 1007878-19-4 ]

Yield	Reaction Conditions	Operation in experiment
56%	With sodium cyanoborohydride; acetic acid; potassium hydroxide; In methanol; at 0 - 20℃;	A mixture of <strong>[53934-78-4](R)-(-)-D-phenylglycine tert-butyl ester</strong> (3.00 g, 12.3 mmol), NaBH3CN (0.773 g, 12.3 mmol), KOH (0.690 g, 12.3 mmol) and acetic acid (0.352 mL, 6.15 mmol) were stirred in methanol at 0 C. To this mixture was added glutaric dialdehyde (2.23 mL, 12.3 mmol) dropwise over 5 minutes. The reaction mixture was stirred as it was allowed to warm to ambient temperature and stirring was continued at the same temperature for 16 hours. The solvent was subsequently removed and the residue was partitioned with 10% aqueous NaOH and ethyl acetate. The organic phase was separated, dried (MgSO4), filtered and concentrated to dryness to provide a clear oil. This material was purified by reverse-phase preparative HPLC (Primesphere C-18, 30×100 mm; CH3CN-H2O-0.1% TFA) to give the intermediate ester (2.70 g, 56%) as a clear oil. 1H NMR (400 MHz, CDCl3) delta 7.53-7.44 (m, 3H), 7.40-7.37 (m, 2H), 3.87 (d, J=10.9 Hz, 1H), 3.59 (d, J=10.9 Hz, 1H), 2.99 (t, J=11.2 Hz, 1H), 2.59 (t, J=11.4 Hz, 1H), 2.07-2.02 (m, 2H), 1.82 (d, J=1.82 Hz, 3H), 1.40 (s, 9H). LC/MS: Anal. Calcd. for C17H25NO2: 275; found: 276 (M+H)+.
56%	With sodium cyanoborohydride; acetic acid; potassium hydroxide; In methanol; at 0 - 20℃;	Step 1 : A mixture of (R)-(-)-D-phenyl glycine tert-butyl ester (3.00 g, 12.3 mmol), NaBH3CN (0.773 g, 12.3 mmol), KOH (0.690 g, 12.3 mmol) and acetic acid (0.352 mL, 6.15 mmol) were stirred in methanol at 0 0C. To this mixture was added glutaric dialdehyde (2.23 rnL, 12.3 mmo.) dropwise over 5 minutes. The reaction mixture was stirred as it was allowed to warm to ambient temperature and stirring was continued at the same temperature for 16 hours. The solvent was subsequently removed and the residue was partitioned with 10% aqueous NaOH and ethyl acetate. The organic phase was separated, dried (MgSO4), filtered and concentrated to dryness to provide a clear oil. This material was purified by reverse-phase preparative HPLC (Primesphere C-18, 30 x 100mm; CH3CN-H2O-0.1% TFA) to give the intermediate ester (2.70 g, 56%) as a clear oil. 1H NMR (400 MHz, CDCl3) delta 7.53-7.44 (m, 3H), 7.40-7.37 (m, 2H)5 3.87 (d, /=10.9 Hz, IH), 3.59 (d, /=10.9 Hz, IH), 2.99 (t, J-11.2 Hz, IH), 2.59 (t, J=I 1.4 Hz, IH), 2.07-2.02 (m, 2H), 1.82 (d, /=1.82 Hz, 3H), 1.40 (s, 9H). LC/MS: Anal. Calcd. for C17H25NO2: 275; found: 276 (M+H)+.
56%	With sodium cyanoborohydride; acetic acid; potassium hydroxide; In methanol; at 0 - 20℃;	A mixture of (R) ~ ( - ) ~D-phenylglycine tert- butyl ester (3.0O g, 12.3 mmol) , NaBH3CN (0.773 g, 12.3 mmol), KOH (0.690 g, 12.3 mmol) and acetic acid (0.352 mli, 6.15 mmol) were stirred in methanol at 0 0C. To this mixture was added glutaric dialdehyde (2.23 mL, 12.3 mmol) dropwise over 5 minutes. The reaction mixture was stirred as it was allowed to warm to ambient temperature and stirring was continued at the same temperature for 16 hours. The solvent was subsequently removed and the residue was partitioned with 10% aqueous NaOH and ethyl acetate. The organic phase was separated, dried (MgSO4) , filtered and concentrated to dryness to provide a clear oil. This material was purified by reverse-phase preparative HPLC (Primesphere C-18, 30 x 100mm; CH3CN- H2O-O.1% TFA) to give the intermediate ester (2.70 g, 56%) as a clear oil. 1H NMR (400 MHz, CDCl3) delta 7.53-7.44 (m, 3H), 7.40-7.37 (m, 2H), 3.87 (d, J=IO.9 Hz, IH), 3.59 (d, J=IO.9 Hz, IH), 2.99 (t, J=Il.2 Hz, IH), 2.59 (t, J=Il.4 Hz, IH), 2.07-2.02 (m, 2H), 1.82 (d, J=I.82 Hz, 3H), 1.40 (s, 9H) . LC/MS: Anal. Calcd. for C17H25NO2: 275; found: 276 (M+H}+.

56%		A mixture of <strong>[53934-78-4](R)-(-)-D-phenylglycine tert-butyl ester</strong> (3.00 g, 12.3 mmol), NaBH3CN (0.773 g, 12.3 mmol), KOH (0.690 g, 12.3 mmol) and acetic acid(0.352 mL, 6.15 mmol) were stirred in methanol at 0 0C. To this mixture was added glutaric dialdehyde (2.23 mL, 12.3 mmol) dropwise over 5 minutes. The reaction mixture was stirred as it was allowed to warm to ambient temperature and stirring was continued at the same temperature for 16 hours. The solvent was subsequently removed and the residue was partitioned with 10% aqueous NaOH and ethyl acetate, The organic phase was separated, dried (MgSO^, filtered and concentrated to dryness to provide a clear oil. This material was purified by reverse-phase preparative HPLC (Primesphere C-18, 30 x 100mm; CH3CN-H2O-0.1% TFA) to give the intermediate ester (2.70 g, 56%) as a clear oil. 1H NMR (400 MHz, CDCl3) delta 7.53-7.44 (m, 3H), 7.40-7.37 (m, 2H), 3.87 (d, 7=10.9 Hz, IH), 3.59 (d, 7=10.9 Hz, IH), 2.99 (t, 7=11.2 Hz, IH), 2.59 (t, 7=11.4 Hz, IH), 2.07-2.02 (m, 2H)5 1.82 (d, 7=1.82 Hz, 3H), 1.40 (s, 9H). LC/MS: Anal. Calcd. for CnH25NO2: 275; found: 276 (M+H)+.
56%	With sodium cyanoborohydride; acetic acid; potassium hydroxide; In methanol; at 0 - 20℃; for 16h;	Step 1 : A mixture of <strong>[53934-78-4](R)-(-)-D-phenylglycine tert-butyl ester</strong> (3.00 g, 12.3 mmol), NaBH3CN (0.773 g, 12.3 mmol), KOH (0.690 g, 12.3 mmol) and acetic acid (0.352 mL, 6.15 mmol) were stirred in methanol at 0 0C. To this mixture was added glutaric dialdehyde (2.23 mL, 12.3 mmol) dropwise over 5 minutes. The reaction mixture was stirred as it was allowed to warm to ambient temperature and stirring was continued at the same temperature for 16 hours. The solvent was subsequently removed and the residue was partitioned with 10% aqueous NaOH and ethyl acetate. The organic phase was separated, dried (MgS O4), filtered and concentrated to dryness to provide a clear oil. This material was purified by reverse-phase preparative HPLC (Primesphere C- 18, 30 x 100mm; CH3CN-H2O-0.1% TFA) to give the intermediate ester (2.70 g, 56%) as a clear oil. 1H NMR (400 MHz, CDCl3) delta 7.53-7.44 (m, 3H),7.40-7.37 (m, 2H), 3.87 (d, J-10.9 Hz, IH), 3.59 (d, J-10.9 Hz, IH), 2.99 (t, J=I 1.2 Hz, IH), 2.59 (t, J=I 1.4 Hz5 IH), 2.07-2.02 (m, 2H), 1.82 (d, J=I .82 Hz, 3H), 1.40 (s,9H). LC/MS: Anal. Calcd. for C17H25NO2: 275; found: 276 (M+H)+.
56%	With sodium cyanoborohydride; acetic acid; potassium hydroxide; In methanol; at 0 - 20℃;	Step 1 : A mixture of <strong>[53934-78-4](R)-(-)-D-phenylglycine tert-butyl ester</strong> (3.00 g, 12.3 mmol), NaBH3CN (0.773 g, 12.3 mmol), KOH (0.690 g, 12.3 mmol) and acetic acid (0.352 mL, 6.15 mmol) were stirred in methanol at 0 C. To this mixture was added glutaric dialdehyde (2.23 mL, 12.3 mmol) dropwise over 5 minutes. The reaction mixture was stirred as it was allowed to warm to ambient temperature and stirring was continued at the same temperature for 16 hours. The solvent was subsequently removed and the residue was partitioned with 10% aqueous NaOH and ethyl acetate. The organic phase was separated, dried (MgS04), filtered and concentrated to dryness to provide a clear oil. This material was purified by reverse-phase preparative HPLC (Primesphere C-18, 30 x 100mm; CH3CN-H2O-0.1% TFA) to give the intermediate ester (2.70 g, 56%) as a clear oil. XH NMR (400 MHz, CDC13) delta 7.53-7.44 (m, 3H), 7.40-7.37 (m, 2H), 3.87 (d, J= 10.9 Hz, IH), 3.59 (d, J= 10.9 Hz, IH), 2.99 (t, J=l 1.2 Hz, IH), 2.59 (t, J= 11.4 Hz, IH), 2.07-2.02 (m, 2H), 1.82 (d, J= 1.82 Hz, 3H), 1.40 (s, 9H). LC/MS: Anal. Calcd. for Ci7H25 02: 275; found: 276 (M+H)+.
56%		A mixture of <strong>[53934-78-4](R)-(-)-D-phenylglycine tert-butyl ester</strong> (3.00 g, 12.3 mmol), NaBH3CN (0.773 g, 12.3 mmol), KOH (0.690 g, 12.3 mmol) and acetic acid (0.352 mL, 6.15 mmol) were stirred in methanol at 0 C. To this mixture was added glutaric dialdehyde (2.23 mL, 12.3 mmol) dropwise over 5 minutes. The reaction mixture was stirred as it was allowed to warm to ambient temperature and stirring was continued at the same temperature for 16 hours. The solvent was subsequently removed and the residue was partitioned with 10% aqueous NaOH and ethyl acetate. The organic phase was separated, dried (MgSC^), filtered and concentrated to dryness to provide a clear oil. This material was purified by reverse-phase preparative HPLC (Primesphere C-18, 30 x 100mm; CH3CN-H2O-0.1% TFA) to give the intermediate ester (2.70 g, 56%) as a clear oil. 1H NMR (400 MHz, CDC13) delta 7.53-7.44 (m, 3H), 7.40-7.37 (m, 2H), 3.87 (d, J=10.9 Hz, IH), 3.59 (d, J= 10.9 Hz, IH), 2.99 (t, J=1 1.2 Hz, IH), 2.59 (t, J= 11.4 Hz, IH), 2.07- 2.02 (m, 2H), 1.82 (d, J=1.82 Hz, 3H), 1.40 (s, 9H). LC/MS: Anal. Calcd. for C17H25NO2: 275; found: 276 (M+H)+.
56%	With sodium cyanoborohydride; acetic acid; potassium hydroxide; In methanol; at 0 - 20℃; for 1h;	[00149] Step 1 : A mixture of <strong>[53934-78-4](R)-(-)-D-phenylglycine tert-butyl ester</strong> (3.00 g, 12.3 mmol), NaBH3CN (0.773 g, 12.3 mmol), KOH (0.690 g, 12.3 mmol) and acetic acid (0.352 mL, 6.15 mmol) were stirred in methanol at 0 C. To this mixture was added glutaric dialdehyde (2.23 mL, 12.3 mmol) dropwise over 5 minutes. The reaction mixture was stirred as it was allowed to warm to ambient temperature and stirring was continued at the same temperature for 16 hours. The solvent was subsequently removed and the residue was partitioned with 10% aqueous NaOH and ethyl acetate. The organic phase was separated, dried (MgS04), filtered and concentrated to dryness to provide a clear oil. This material was purified by reverse-phase preparative HPLC (Primesphere C-18, 30 x 100mm; CH3CN-H2O-0.1% TFA) to give the intermediate ester (2.70 g, 56%) as a clear oil. 'H NMR (400 MHz, CDC13) delta 7.53-7.44 (m, 3H), 7.40-7.37 (m, 2H), 3.87 (d, J= 10.9 Hz, 1H), 3.59 (d, J=10.9 Hz, 1H), 2.99 (t, J= 11.2 Hz, 1H), 2.59 (t, J= 11.4 Hz, 1H), 2.07- 2.02 (m, 2H), 1.82 (d, J= 1.82 Hz, 3H), 1.40 (s, 9H). LC-MS: Anal. Calcd. forCi7H25 02: 275; found: 276 (M+H)+.
56%	With sodium cyanoborohydride; acetic acid; potassium hydroxide; In methanol; at 0 - 20℃; for 16h;	Step 1: A mixture of <strong>[53934-78-4](R)-(-)-D-phenylglycine tert-butyl ester</strong> (3.00 g, 12.3 mmol), NaBH3CN (0.773 g, 12.3 mmol), KOH (0.690 g, 12.3 mmol) and acetic acid (0.352 mL, 6.15 mmol) were stirred in methanol at 0 C. To this mixture was added glutaric dialdehyde (2.23 mL, 12.3 mmol) dropwise over 5 minutes. The reaction mixture was stirred as it was allowed to warm to ambient temperature and stirring was continued at the same temperature for 16 hours. The solvent was subsequently removed and the residue was partitioned with 10% aqueous NaOH and ethyl acetate. The organic phase was separated, dried (MgSC^), filtered and concentrated to dryness to provide a clear oil. This material was purified by reverse-phase preparative HPLC (Primesphere C-18, 30 x 100mm; CH3CN-H2O-0.1% TFA) to give the intermediate ester (2.70 g, 56%) as a clear oil. XH NMR (400 MHz, CDC13) delta 7.53-7.44 (m, 3H), 7.40-7.37 (m, 2H), 3.87 (d, J= 10.9 Hz, 1H), 3.59 (d, J= 10.9 Hz, 1H), 2.99 (t, J= 11.2 Hz, 1H), 2.59 (t, J= 1 1.4 Hz, 1H), 2.07-2.02 (m, 2H), 1.82 (d, J= 1.82 Hz, 3H), 1.40 (s, 9H). LC/MS: Anal. Calcd. for Ci7H25 02: 275; found: 276 (M+H)+.
56%	With sodium cyanoborohydride; acetic acid; potassium hydroxide; In methanol; at 20℃; for 16h;	A mixture of <strong>[53934-78-4](R)-(-)-D-phenylglycine tert-butyl ester</strong> (3.00 g, 12.3 mmol), NaBH3CN (0.773 g, 12.3mmol), KOH (0.690 g, 12.3 mmol) and acetic acid (0.352 mL, 6.15 mmol) were stirred in methanol at 0 C. To this mixturewas added glutaric dialdehyde (2.23 mL, 12.3 mmol) dropwise over 5 minutes. The reaction mixture was stirred as itwas allowed to warm to ambient temperature and stirring was continued at the same temperature for 16 hours. Thesolvent was subsequently removed and the residue was partitioned with 10% aqueous NaOH and ethyl acetate. Theorganic phase was separated, dried (MgSO4), filtered and concentrated to dryness to provide a clear oil. This materialwas purified by reverse-phase preparative HPLC (Primesphere C-18, 30 x 100mm; CH3CN-H2O-0.1% TFA) to give theintermediate ester (2.70 g, 56%) as a clear oil. 1H NMR (400 MHz, CDCl3) delta 7.53-7.44 (m, 3H), 7.40-7.37 (m, 2H), 3.87(d, J=10.9 Hz, 1H), 3.59 (d, J=10.9 Hz, 1H), 2.99 (t, J=11.2 Hz, 1H), 2.59 (t, J=11.4 Hz, 1H), 2.07-2.02 (m, 2H), 1.82 (d,J=1.82 Hz, 3H), 1.40 (s, 9H). LC/MS: Anal. Calcd. for C17H25NO2: 275; found: 276 (M+H)+.
56%	With potassium hydroxide; sodium cyanoborohydride; acetic acid; In methanol; at 0 - 20℃; for 16.0833h;	A mixture of <strong>[53934-78-4](R)-(-)-D-phenylglycine tert-butyl ester</strong> (3.00 g, 12.3 mmol), NaBH3CN (0.773 g, 12.3 mmol), KOH (0.690 g, 12.3 mmol) and acetic acid (0.352 mL, 6.15 mmol) were stirred in methanol at 0 C. To this mixture was added glutaric dialdehyde (2.23 mL, 12.3 mmol) dropwise over 5 minutes. The reaction mixture was stirred as it was allowed to warm to ambient temperature and stirring was continued at the same temperature for 16 hours. The solvent was subsequently removed and the residue was partitioned with 10% aqueous NaOH and ethyl acetate. The organic phase was separated, dried (MgSO4), filtered and concentrated to dryness to provide a clear oil. This material was purified by reverse-phase preparative HPLC (Primesphere C-18, 30×100 mm; CH3CN-H2O-0.1% TFA) to give the intermediate ester (2.70 g, 56%) as a clear oil. 1HNMR (400 MHz, CDCl3) delta 7.53-7.44 (m, 3H), 7.40-7.37 (m, 2H), 3.87 (d, J=10.9 Hz, 1H), 3.59 (d, J=10.9 Hz, 1H), 2.99 (t, J=11.2 Hz, 1H), 2.59 (t, J=11.4 Hz, 1H), 2.07-2.02 (m, 2H), 1.82 (d, J=1.82 Hz, 3H), 1.40 (s, 9H). LC/MS: Anal. Calcd. for C17H25NO2: 275; found: 276 (M+H)+.
56%	With potassium hydroxide; sodium cyanoborohydride; acetic acid; In methanol; at 0 - 20℃; for 16.0833h;	Step 1: A mixture of <strong>[53934-78-4](R)-(-)-D-phenylglycine tert-butyl ester</strong> (3.00 g, 12.3 mmol), NaBH3CN (0.773 g, 12.3 mmol), KOH (0.690 g, 12.3 mmol) and acetic acid (0.352 mL, 6.15 mmol) were stirred in methanol at 0 C. To this mixture was added glutaric dialdehyde (2.23 mL, 12.3 mmol) dropwise over 5 minutes. The reaction mixture was stirred as it was allowed to warm to ambient temperature and stirring was continued at the same temperature for 16 hours. The solvent was subsequently removed and the residue was partitioned with 10% aqueous NaOH and ethyl acetate. The organic phase was separated, dried (MgSO4), filtered and concentrated to dryness to provide a clear oil. This material was purified by reverse-phase preparative HPLC (Primesphere C-18, 30×100 mm; CH3CN-H2O-0.1% TFA) to give the intermediate ester (2.70 g, 56%) as a clear oil. 1HNMR (400 MHz, CDCl3) delta 7.53-7.44 (m, 3H), 7.40-7.37 (m, 2H), 3.87 (d, J=10.9 Hz, 1H), 3.59 (d, J=10.9 Hz, 1H), 2.99 (t, J=11.2 Hz, 1H), 2.59 (t, J=11.4 Hz, 1H), 2.07-2.02 (m, 2H), 1.82 (d, J=1.82 Hz, 3H), 1.40 (s, 9H). LC/MS: Anal. Calcd. for C17H25NO2: 275; found: 276 (M+H)+.
56%	With potassium hydroxide; sodium cyanoborohydride; acetic acid; In methanol; at 0 - 20℃; for 16.0833h;	A mixture of <strong>[53934-78-4](R)-(-)-D-phenylglycine tert-butyl ester</strong> (3.00 g, 12.3 mmol), NaBH3CN (0.773 g, 12.3 mmol), KOH (0.690 g, 12.3 mmol) and acetic acid (0.352 mL, 6.15 mmol) were stirred in methanol at 0 0C. To this mixture was added glutaric dialdehyde (2.23 mL, 12.3 mmol) dropwise over 5 minutes. The reaction mixture was stirred as it was allowed to warm to ambient temperature and stirring was continued at the same temperature for 16 hours. The solvent was subsequently removed and the residue was partitioned with 10% aqueous NaOH and ethyl acetate. The organic phase was separated, dried (MgSO4), filtered and concentrated to dryness to provide a clear oil. This material was purified by reverse-phase <n="58"/>preparative HPLC (Primesphere C-18, 30 x 100mm; CH3CN-H2O-0.1% TFA) to give the intermediate ester (2.70 g, 56%) as a clear oil. 1H NMR (400 MHz, CDCl3) delta 7.53-7.44 (m, 3H), 7.40-7.37 (m, 2H), 3.87 (d, J= 10.9 Hz, IH), 3.59 (d, J= 10.9 Hz, IH), 2.99 (t, J=I 1.2 Hz, IH), 2.59 (t, J=I 1.4 Hz, IH), 2.07-2.02 (m, 2H), 1.82 (d, J= 1.82 Hz, 3H), 1.40 (s, 9H). LC/MS: Anal. Calcd. for Ci7H25NO2: 275; found: 276 (M+H)+.
56%		Step 1: A mixture of <strong>[53934-78-4](R)-(-)-D-phenylglycine tert-butyl ester</strong> (3.00 g, 12.3 mmol), NaBH3CN (0.773 g, 12.3 mmol), KOH (0.690 g, 12.3 mmol) and acetic acid (0.352 mL, 6.15 mmol) were stirred in methanol at 0 0C. To this mixture was added glutaric dialdehyde (2.23 mL, 12.3 mmol) dropwise over 5 minutes. The reaction mixture was stirred as it was allowed to warm to ambient temperature and stirring was continued at the same temperature for 16 hours. The solvent was subsequently removed and the residue was partitioned with 10% aqueous NaOH and ethyl acetate. The organic phase was separated, dried (MgSO4), filtered and concentrated to dryness to provide a clear oil. This material was purified by reverse-phase <n="53"/>preparative HPLC (Primesphere C-18, 30 x 100mm; CH3CN-H2O-0.1% TFA) to give the intermediate ester (2.70 g, 56%) as a clear oil. 1HNMR (400 MHz, CDCl3) delta 7.53-7.44 (m, 3H), 7.40-7.37 (m, 2H), 3.87 (d, J = 10.9 Hz, IH), 3.59 (d, J = 10.9 Hz, IH), 2.99 (t, J = 11.2 Hz, IH), 2.59 (t, J = 11.4 Hz, IH), 2.07-2.02 (m, 2H), 1.82 (d, J = 1.82 Hz, 3H), 1.40 (s, 9H). LC/MS: Anal. Calcd. for Ci7H25NO2: 275; found: 276 (M+H)+.
56%	With sodium cyanoborohydride; acetic acid; potassium hydroxide; In methanol; at 0 - 20℃;	Step 1: A mixture of <strong>[53934-78-4](R)-(-)-D-phenylglycine tert-butyl ester</strong> (3.00 g, 12.3 mmol), NaBH3CN (0.773 g, 12.3 mmol), KOH (0.690 g, 12.3 mmol) and acetic acid (0.352 mL, 6.15 mmol) were stirred in methanol at 0 C. To this mixture was added glutaric dialdehyde (2.23 mL, 12.3 mmol) dropwise over 5 minutes. The reaction mixture was stirred as it was allowed to warm to ambient temperature and stirring was continued at the same temperature for 16 hours. The solvent was subsequently removed and the residue was partitioned with 10% aqueous NaOH and ethyl acetate. The organic phase was separated, dried (MgSO4), filtered and concentrated to dryness to provide a clear oil. This material was purified by reverse-phase preparative HPLC (Primesphere C-18, 30×100mm; CH3CN-H2O-0.1% TFA) to give the intermediate ester (2.70 g, 56%) as a clear oil. 1H NMR (400 MHz, CDCl3) delta 7.53-7.44 (m, 3H), 7.40-7.37 (m, 2H), 3.87 (d, J=10.9 Hz, 1H), 3.59 (d, J=10.9 Hz, 1H), 2.99 (t, J=11.2 Hz, 1H), 2.59 (t, J=11.4 Hz, 1H), 2.07-2.02 (m, 2H), 1.82 (d, J=1.82 Hz, 3H), 1.40 (s, 9H). LC/MS: Anal. Calcd. for C17H25NO2: 275; found: 276 (M+H)+.
56%	With sodium cyanoborohydride; acetic acid; potassium hydroxide; In methanol; at 0 - 20℃;	Cap- 14; Step 1: A mixture of (R)-(-)-D-phenylglycme tert-butyl ester (3.00 g, 12.3 rnmol), NaBH3CN (0.773 g, 12.3 mmol), KOH (0.690 g, 12.3 mmol) and acetic acid (0.352 mL, 6.15 mmol) were stirred in methanol at 0 0C. To this mixture was added glutaric dialdehyde (2.23 mL, 12.3 mmol) dropwise over 5 minutes. The reaction mixture was stirred as it was allowed to warm to ambient temperature and stirring was continued at the same temperature for 16 hours. The solvent was subsequently removed and the residue was partitioned with 10% aqueous NaOH and ethyl acetate. The organic phase was separated, dried (MgSO4), filtered and concentrated to dryness to provide a clear oil. This material was purified by reverse-phase preparative HPLC (Primesphere C-18, 30 x 100mm; CH3CN-H2O-0.1% TFA) to give the intermediate ester (2.70 g, 56%) as a clear oil. 1H NMR (400 MHz3 CDCl3) 57.53-7.44 (m, 3H), 7.40-7.37 (m, 2H), 3.87 (d, J-10.9 Hz, IH), 3.59 (d, J=10.9 Hz5 IH), 2.99 (t, J=I 1.2 Hz, IH), 2.59 (t, J=I 1.4 Hz, IH)5 2.07-2.02 (m, 2H), 1.82 (d, J=I .82 Hz, 3H), 1.40 (s, 9H). LC/MS: Anal. Calcd. for Ci7H25NO2: 275; found: 276 (M+H)+.

Reference： [1]Patent: US2009/233925,2009,A1 .Location in patent: Page/Page column 22-23
[2]Patent: WO2010/17401,2010,A1 .Location in patent: Page/Page column 194-195
[3]Patent: WO2010/120621,2010,A1 .Location in patent: Page/Page column 94
[4]Patent: WO2010/138488,2010,A1 .Location in patent: Page/Page column 87-88
[5]Patent: WO2010/138368,2010,A1 .Location in patent: Page/Page column 46
[6]Patent: WO2011/60000,2011,A1 .Location in patent: Page/Page column 131-132
[7]Patent: WO2011/59850,2011,A1 .Location in patent: Page/Page column 46
[8]Patent: WO2011/75439,2011,A1 .Location in patent: Page/Page column 41-42
[9]Patent: WO2012/18325,2012,A1 .Location in patent: Page/Page column 44
[10]Patent: EP2328865,2017,B1 .Location in patent: Paragraph 0364-0365
[11]Patent: US2008/44379,2008,A1 .Location in patent: Page/Page column 38
[12]Patent: US2008/44380,2008,A1 .Location in patent: Page/Page column 36-37
[13]Patent: WO2008/144380,2008,A1 .Location in patent: Page/Page column 55-56
[14]Patent: WO2009/102318,2009,A1 .Location in patent: Page/Page column 51-52
[15]Patent: US2010/249190,2010,A1 .Location in patent: Page/Page column 31
[16]Patent: WO2010/117635,2010,A1 .Location in patent: Page/Page column 165

9
tert-butyl (R)-2-((tert-butoxycarbonyl)amino)-2-phenylacetate [ No CAS ]
[ 53934-78-4 ]

Reference： [1]Journal of the American Chemical Society,2007,vol. 129,p. 12066 - 12067

10
[ 53934-78-4 ]
[ 208255-80-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 1983 - 1985

11
[ 53934-78-4 ]
(R)-[(R)-Cyclohexyl-(diethoxy-phosphoryl)-methyl]-amino}-phenyl-acetic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1995,vol. 117,p. 10879 - 10888

12
[ 53934-78-4 ]
(R)-[(S)-Cyclohexyl-(diethoxy-phosphoryl)-methyl]-amino}-phenyl-acetic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1995,vol. 117,p. 10879 - 10888

13
[ 646036-87-5 ]
[ 53934-78-4 ]
1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-{4-{N-[(R)-α-(t-butoxycarbonyl)benzyl]carbamoylmethoxy}phenyl}azetidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 2,6-dimethylpyridine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; In dichloromethane; at 20℃; for 5h;	1- (4-FLUOROPHENYL)-3- [3- (4-FLUOROPHENYL)-3-HYDROXYPROPYL]-4- (4-CARBOXYMETHOXY] phenyl) azetidin-2-one (Method 1; 40 mg, 0.086 mmol [TERT-BUTYL] (2amino (phenyl) acetate (20 mg, 0.095 mmol) and 2,6-lutidine (50 [1,] 0.42 mmol) were added to DCM (3 [ML).] TBTU (36 mg, 0.11 mmol) was added and the mixture was stirred at room temperature for 5 hours. The solvent was evaporated under reduced pressure and was co-evaporated with toluene. The residue was purified by column chromatography using [DCM/ETOAC] [(10/2)] as eluent to give the title compound. M/z 655.3 [(M-H)-.]

Reference： [1]Patent: WO2004/5247,2004,A1 .Location in patent: Page 84

14
[ 858104-50-4 ]
[ 53934-78-4 ]
C₃₇H₃₄F₂N₂O₆S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Method 4; (2R)-({ ([4-((2R,3R)-1-(4-fluorophenyl)-3-[2-(4-fluorophenyl)-2-oxoethyl]thio}-4- oxoazetidin-2-yl) phenoxy] acetyl} amino) (phenyl) acetic acid; [4-((2R,3R)-1-(4-Fluorophenyl)-3-[2-(4-fluorophenyl)-2-oxoethyl]thio]-4-oxoazetidin-2- yl) phenoxy] acetic acid (0.40 g, 0.827 mmol) was dissolved in CH2C12 (40 ml) and tert-butyl (2amino (phenyl) acetate (0.206 g, 0.993 mmol) and N-methylmorpholine (0.251 g, 2.48 mmol) were added. After 10 minutes, TBTU (0.345 g, 1.076 mmol) was added. The reaction was stirred overnight. The resulting tert-butyl ester was concentrated and purified on silica gel (eluted with EtOAc/CH2C12 25/75). The pure fractions were collected and concentrated. CH2C12 (25 ml) and TFA (3 ml) were added. The mixture was stirred for 5 days and the solvent was removed under reduced pressure. The residue was purified by preparative HPLC using a gradient of 20-70% CH3CN in 0. 1M NH4OAc buffer. Freeze-drying of the pure fractions gave the title compound as a colourless solid. M/z : 615.50 (M-l). lH NMR [(CD3) 2SO), 400 MHz] 8 4.35 (d, 1H), 4.36 (d, 1H), 4.40 (d, 1H), 4.53 (d, 1H), 4.58 (d, 1H), 4.94 (d, 1H), 5.19 (d, 1H), 6.97-7. 40 (m, 15H), 8.02-8. 06 (m, 2H), 8.26-8. 32 (m, 1H).

Reference： [1]Patent: WO2005/61452,2005,A1 .Location in patent: Page/Page column 129-130

15
[ 858104-55-9 ]
[ 53934-78-4 ]
C₃₉H₃₇F₂N₃O₇S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 4-methyl-morpholine; (1,1,1-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate; In dichloromethane; at 20℃; for 1.5h;	Example 1; (2R)-[(N-[[4-((2R,3R)-1-(4-fluorophenyl)-3-[2-(4-fluorophenyl)-2-hydroxyethyl]thio}-4- oxoazetidin-2-yl)phenoxy]acetyl}glycyl)amino](phenyl) acetic acid; N-[4-((2R,3R)-1-(4-fluorophenyl)-3-[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2- yl) phenoxy] acetyl} glycine (44 mg, 0.081 mmol), N-methylmorpholine (18 ul, 0.16 mmol), tert-butyl (2amino (phenyl) acetate (23 mg, 0.11 mmol) and TBTU (36 mg, 0.11 mmol) were added to methylene chloride (3 ml) and the reaction mixture was sirred at ambient temperature for 1.5 h. The mixture was purified by column chromatography on silica gel using methylene chloride/ethylacetate (1/1) as eluent. The resulting intermediate ester was dissolved in formic acid (2 ml) and the mixture was stirred overnight at 45 C. The solvent was evaporated under reduced pressure and was co-evaporated with toluene. The residue was dissolved in methanol (2 ml) and NaBH4 10 mg, 0.26 mmol) was added. The reaction mixture was stirred at ambient temperature for 15 min. A small amount of ammoniumacetate buffer was added and the methanol was evaporated off. The residue was purified by preparativ HPLC using acetonitril/ammonium acetat buffer (45: 55) as eluent. The collected fractions were lyophilized to obtain 39 mg (71%, 3 steps) of the title compound. (1H-NMR, 400 MHz, CD30D) : 1.8-2. 0 (m, 2H), 3.75 (d, 2H), 4.3 (d, 1H), 4.55 (s, 2H), 4.65-4. 80 (m, 2H), 5.05 (d, 1H), 7.0-7. 4 (m, 17 H), 7.95 (dd, 1H) 8. 25 (t, 1H)

Reference： [1]Patent: WO2005/61452,2005,A1 .Location in patent: Page/Page column 57-58

16
[ 858103-93-2 ]
[ 53934-78-4 ]
C₄₅H₄₁F₂N₃O₇S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 10; (2R)-[(2R)-2-([4-((2R,3R)-1-(4-fluorophenyl)-3-[2-(4-fluorophenyl)-2- hydroxyethyl] thio}-4-oxoazetidin-2-yl) phenoxy] acetyl} amino)-2- phenylacetyl] amino} (phenyl) acetic acid; (2R)- ( { [4- ( (2R, 3R)-1- (4-Fluorophenyl)-3- { [2- (4-fluorophenyl)-2-oxoethyl] thio}-4- oxoazetidin-2-yl) phenoxy] acetyl} amino) (phenyl) acetic acid (0.040 g, 0.065 mmol) was dissolved in CH2C12 (5 ml) and tert-butyl (2amino (phenyl) acetate (0.016 g, 0. 078 mmol) and N-methyl-morphiline (0.020 g, 0.195 mmol) were added. After 5 minutes TBTU (0.027 g, 0.084 mmol) was added. The reaction was allowed to stir at room temperature for 3 h after which the resulting tert-butyl ester was purified on silica gel and eluted with EtOAc/CH2C12 25/75. Pure fractions were concentrated. The residue was dissolved in CH2C12 (3 ml) and TFA (0.5 ml). The reaction mixture was allowed to stir overnight at room temperature. The resulting acid was concentrated and the remaining trace of TFA was removed by co- evaporation with toluene (3 ml). The acid was dissolved in MeOH (3 ml) and NaBH4 (0.010 g, 0.260 mmol) was added. After 5 minutes, full conversion to the corresponding alcohol was obtained. The reaction was quenched by the addition of 1 ml of 0. 1M NBLtOAc buffer. Concentration followed by purification on preparative HPLC using a gradient of 20-50% CH3CN in 0. 1M NH4OAc buffer as mobile phase and freeze-drying of the pure fractions afforded the title compound (0.034 g, 70%) as a colourless solid. M/z : 750.4 (M-1). 1H NMR [(CD3) 2SO), 400 MHz] 8 2.88-2. 94 (m, 2H), 4.23-4. 29 (m, 1H), 4.56-4. 65 (m, 2H), 4.70-4. 78 (m, 1H), 4.91-5. 06 (m, 2H), 5. 65-5. 75 (m, 1H), 6.93-7. 42 (m, 22H), 8. 54-8.69 (m, 2H).

Reference： [1]Patent: WO2005/61452,2005,A1 .Location in patent: Page/Page column 64-65

17
[ 501692-63-3 ]
[ 53934-78-4 ]
[ 501692-67-7 ]

Yield	Reaction Conditions	Operation in experiment
91%	With 2,6-dimethylpyridine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; In dichloromethane; for 3.5h;	Method 2 1, l-Dioxo-3, 3-dibutY1-5-phenyl-7-methYlthio-8-{N-r (R)-oc-(t-butoxycarbonyl) ben carbamovlmethoxy}-2, 3. 4, 5-tetrahvdro-1, 2. 5-benzothiadiazepine 1, 1-Dioxo-3, 3-dibutyl-5-phenyl-7-methylthio-8-carboxymethoxy-2,3, 4,5-tetrahydro- 1,2, 5-benzothiadiazepine (Method 3; 627 mg, 1.24 mmol) was dissolved in DCM (25 ml), tert-butyl (2R) -amino (phenyl) acetate (308 mg, 1. 48 mmol, 2,6-dimethylpyridine (288 1, 2.47 mmol) and TBTU (477 mg, 1. 48 mmol) were added. The mixture was stirred for 3.5 hours. The reaction mixture was evaporated under reduced pressure. The product was purified using an Isolute column (lOg, silica). The product was eluted with a stepwise gradient using DCM: EtOAc 100: 0 then 95: 5. Approximately 694mg pure compound was collected. An additional fraction was purified a second time using an Isolute column (lOg, silica). The product was eluted with a stepwise gradient using DCM: EtOAc 100: 0,95 : 5 then 90: 10. The pure fraction was added to the first fraction yielding 787 mg (91%) of the title compound. NMR (400MHz, CDC13) 0.78 (t, 6H), 0.92-1. 12 (m, 4H), 1.12-1. 46 (m, 6H), 1.54 (s, 9H), 1. 58-1. 72 (m, 2H), 2.14 (s, 3H), 3. 8-4. 05 (m, 2H), 4.32 (brs, NH), 4.56 (ABq, 2H), 5.56 (d, 1H), 6.56 (s, 1H), 7.04 (t, 1H), 7.10 (brd, 2H) 7.24-7. 42 (m, 8H), 7.84 (d, NH); m/z 694.7 (M- H)-.
91%	With 2,6-dimethylpyridine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; In dichloromethane; at 18 - 25℃; for 3.5h;Inert atmosphere;	Method 9 1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-{N-[(R)-alpha-(t-butoxycarbonyl)benzyl] carbamoylmethoxy}-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine (0190) 1,1-Dioxo-3,3-dibutyl-S-phenyl-7-methylthio-8-carboxymethoxy-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine (Method 3; 627 mg, 1.24 mmol) was dissolved in DCM (25 ml), <strong>[53934-78-4]tert-butyl (2R)-amino(phenyl)acetate</strong> (308 mg, 1.48 mmol), 2,6-dimethylpyridine (288 mul, 2.47 mmol) and TBTU (477 mg, 1.48 mmol) were added. The mixture was stirred for 3.5 hours. The reaction mixture was evaporated under reduced pressure. The product was purified using an Isolute column (10g, silica). The product was eluted with a stepwise gradient using DCM: EtOAc 100:0 then 95:5. Approximately 694mg pure compound was collected. Another fraction was purified a second time using an Isolute column (10g, silica). The product was eluted with a stepwise gradient using DCM:EtOAc 100:0,95:5 then 90:10. The pure fraction was added to the first fraction yielding 787 mg (91%) of the title compound. NMR (400MHz, CDCl3) 0.78 (t, 6H), 0.92-1.12 (m, 4H), 1.12-1.46 (m, 6H), 1.54 (s, 9H), 1.58-1.72 (m, 2H), 2.14 (s, 3H), 3.8-4.05 (m, 2H), 4.32 (brs, NH), 4.56 (ABq, 2H), 5.56 (d, 1H), 6.56 (s, 1H), 7.04 (t, 1H), 7.10 (brd, 2H) 7.24-7.42 (m, 8H), 7.84 (d, NH); m/z 694.7 (M-H)-.

Reference： [1]Patent: WO2003/91232,2003,A2 .Location in patent: Page/Page column 54-55
[2]Patent: EP1427423,2017,B9 .Location in patent: Paragraph 0190

18
[ 108-48-5 ]
[ 439088-77-4 ]
[ 53934-78-4 ]
[ 439088-78-5 ]

Yield	Reaction Conditions	Operation in experiment
85 mg (89%)	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; In 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; Petroleum ether;	Method 90 1,1-Dioxo-3-butyl-3-ethyl-5-phenyl-7-bromo-8-(2-{N-[(R)-alpha-(t-butoxycarbonyl)benzyl]carbamoyl}ethoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine To a solution of 1,1-dioxo-3-butyl-3-ethyl-5-phenyl-7-bromo-8-(2-carboxyethoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine (Method 89; 70 mg, 0.134 mmol) and (R)-alpha-(t-butoxycarbonyl)benzylamine (J. Amer. Chem. Soc.; EN; 117; 44; 1995; 10879-10888; 35 mg, 0.169 mmol) in DCM (2.5 ml) was added 2,6-lutidine (29 mg, 0.268 mmol) and TBTU (56 mg, 0.174 mmol). The reaction mixture was stirred at room temperature for 2.5 hours, then diluted with DCM. The solution was washed with NaHCO3 (aq, sat), water, dried and the solvent was evaporated under reduced pressure. The residue was suspended in ether/petroleum ether and the crystals filtered to give the title compound 85 mg (89%). NMR (500 MHz) 0.79-0.86 (m, 6H), 1.04-1.28 (m, 4H), 1.35-1.56 (m, 11H), 1.60-1.77 (m, 2H), 2.82 (t, 2H), 3.13-3.25 (m, 2H), 3.72 (brs, 2H), 4.35-4.44 (m, 2H), 5.54 (d, 1H), 6.95 (d, 1H), 7.04 (t, 1H), 7.08 (d, 2H), 7.15:(s, 1H), 7.29-7.43 (m, 6H), 7.52 (s, 1H).

Reference： [1]Patent: US2004/67933,2004,A1

19
[ 53934-78-4 ]
[ 7087-68-5 ]
[ 79-44-7 ]
(R)-tert-butyl 2-(3,3-dimethylureido)-2-phenylacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	In ethyl acetate; N,N-dimethyl-formamide;	Step 1; (R)-tert-butyl 2-(3,3-dimethylureido)-2-phenylacetate: To a stirred solution of <strong>[53934-78-4](R)-tert-butyl-2-amino-2-phenylacetate</strong> (1.0 g, 4.10 mmol) and Hunig's base (1.79 mL, 10.25 mmol) in DMF (40 mL) was added dimethylcarbamoyl chloride (0.38 mL, 4.18 mmol) dropwise over 10 minutes. After stirring at room temperature for 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate. The organic layer was washed with H2O, 1N aq. HCl and brine, dried (MgSO4), filtered and concentrated under reduced pressure. (R)-tert-butyl 2-(3,3-dimethylureido)-2-phenylacetate was obtained as a white solid (0.86 g; 75%) and used without further purification. 1H NMR (500 MHz, DMSO-d6) delta ppm 1.33 (s, 9H) 2.82 (s, 6H) 5.17 (d, J=7.63 Hz, 1H) 6.55 (d, J=7.32 Hz, 1H) 7.24-7.41 (m, 5H). LCMS: Anal. Calcd. for C15H22N2O3 278.16 found 279.23 (M+H)+; HPLC Phenomenex LUNA C-18 4.6*50 mm, 0 to 100% B over 4 minutes, 1 minute hold time, A=90% water, 10% methanol, 0.1% TFA, B=10% water, 90% methanol, 0.1% TFA, RT=2.26 min, 97% homogeneity index.
75%	In ethyl acetate; N,N-dimethyl-formamide;	Step 1; (R)-tert-butyl 2-(3,3-dimethylureido)-2-phenylacetate: To a stirred solution of <strong>[53934-78-4](R)-tert-butyl-2-amino-2-phenylacetate</strong> (1.0 g, 4.10 mmol) and Hunig's base (1.79 mL, 10.25 mmol) in DMF (40 mL) was added dimethylcarbamoyl chloride (0.38 mL, 4.18 mmol) dropwise over 10 minutes. After stirring at room temperature for 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate. The organic layer was washed with H2O, 1N aq. HCl and brine, dried (MgSO4), filtered and concentrated under reduced pressure. (R)-tert-butyl 2-(3,3-dimethylureido)-2-phenylacetate was obtained as a white solid (0.86 g; 75%) and used without further purification. 1H NMR (500 MHz, DMSO-d6) delta ppm 1.33 (s, 9H) 2.82 (s, 6H) 5.17 (d, J=7.63 Hz, 1H) 6.55 (d, J=7.32 Hz, 1H) 7.24-7.41 (m, 5H). LCMS: Anal. Calcd. for C15H22N2O3 278.16 found 279.23 (M+H)+; HPLC Phenomenex LUNA C-18 4.6*50 mm, 0 to 100% B over 4 minutes, 1 minute hold time, A=90% water, 10% methanol, 0.1% TFA, B=10% water, 90% methanol, 0.1% TFA, RT=2.26 min, 97% homogeneity index.
75%	In ethyl acetate; N,N-dimethyl-formamide;	Step 1; (R)-tert-butyl 2-(3,3-dimethylureido)-2-phenylacetate: To a stirred solution of <strong>[53934-78-4](R)-tert-butyl-2-amino-2-phenylacetate</strong> (1.0 g, 4.10 mmol) and Hunig's base (1.79 mL, 10.25 mmol) in DMF (40 mL) was added dimethylcarbamoyl chloride (0.38 mL, 4.18 mmol) dropwise over 10 minutes. After stirring at room temperature for 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate. The organic layer was washed with H2O, 1N aq. HCl and brine, dried (MgSO4), filtered and concentrated under reduced pressure. (R)-tert-butyl 2-(3,3-dimethylureido)-2-phenylacetate was obtained as a white solid (0.86 g; 75%) and used without further purification. 1H NMR (500 MHz, DMSO-d6) 5 ppm 1.33 (s, 9H) 2.82 (s, 6H) 5.17 (d, J=7.63 Hz, 1H) 6.55 (d, J=7.32 Hz, 1H) 7.24-7.41 (m, 5H). LCMS: Anal. Calcd. for C15H22N2O3 278.16 found 279.23 (M+H)+; HPLC Phenomenex LUNA C-18 4.6*50 mm, 0 to 100% B over 4 minutes, 1 minute hold time, A=90% water, 10% methanol, 0.1% TFA, B=10% water, 90% methanol, 0.1% TFA, RT=2.26 min, 97% homogeneity index.

Reference： [1]Patent: US2009/202478,2009,A1
[2]Patent: US2009/202483,2009,A1
[3]Patent: US2010/80772,2010,A1

20
[ 53934-78-4 ]
[ 79-22-1 ]
[ 1007877-76-0 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; water; for 5.6h;Cooling with ice;	ClCO2Me (3.2 mL, 41.4 mmol) was added dropwise to a cooled (ice/water)THF (410 mL) semi-solution of (R)-terf-butyl 2-amino-2-phenylacetate/HCl (9.877 g, 40.52 mmol) and diisopropylethylamine (14.2 mL, 81.52 mmol) over 6 min, and stirred at similar temperature for 5.5 hours. The volatile component was removed in vacuo, and the residue was partitioned between water (100 mL) and ethyl acetate (200 mL). The organic layer was washed with IN HCl (25 mL) and saturated NaHCO^ solution (30 mL), dried (MgSO4), filtered, and concentrated in vacuo. The resultant colorless oil was triturated from hexanes, filtered and washed with hexanes (100 mL) to provide (R)-tert-buty 2-(methoxycarbonylamino)-2-phenylacetate as a white solid (7.7 g). 1H NMR (DMSOd6, delta = 2.5 ppm, 400 MHz): 7.98 (d, /=8.0, IH)5 7.37-7.29 (m, 5H), 5.09 (d, J=8, IH), 3.56 (s, 3H), 1.33 (s, 9H). LC (Con. 7): RT-1.53 min; -90 % homogeneity index; LC/MS: Anal. Calcd. for [M+Na]+ C14H19NNaO4:288.12; found 288.15.
	With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; for 5.6h;Cooling with ice;	ClCO2Me (3.2 mL, 41.4 mmol) was added dropwise to a cooled (ice/water) THF (410 mL) semi-solution of (R)-terf-butyl 2-amino-2~phenylacetate/HCl (9.877 g, 40.52 mmol) and diisopropylethylamine (14.2 mL, 81.52 mmol) over 6 min, and stirred at similar temperature for 5.5 hours. The volatile component was removed in vacuo, and the residue was partitioned between water (100 mL) and ethyl acetate (200 mL). The organic layer was washed with IN HCl (25 mL) and saturated NaHCO3 solution (30 mL), dried (MgSO4), filtered, and concentrated in vacuo. The resultant colorless oil was triturated from hexanes, filtered and washed with hexanes (100 mL) to provide (R)-tert-butyl 2-(methoxycarbonylamino)-2-phenylacetate as a white solid (7.7 g). 1H NMR (DMSO-d6f delta=2.5 ppm, 400 MHz): 7.98 (d, /=8.0, IH), 7.37-7.29 (m, 5H), 5.09 (d, /=8, IH), 3.56 (s, 3H), 1.33 (s, 9H). LC (Cond. I): RT=I.53 min; -90 % homogeneity index; LC/MS: Anal. Calcd. for [M+Naf Ci4H19NNaO4: 288.12; found 288.15.

Reference： [1]Patent: WO2010/138488,2010,A1 .Location in patent: Page/Page column 79-80
[2]Patent: WO2010/117635,2010,A1 .Location in patent: Page/Page column 158

21
[ 53934-78-4 ]
[ 111-30-8 ]
[ 714976-58-6 ]

Reference： [1]Patent: WO2011/59850,2011,A1
[2]Patent: WO2011/75439,2011,A1
[3]Patent: WO2012/18325,2012,A1
[4]Patent: EP2328865,2017,B1
[5]Patent: US2008/44379,2008,A1
[6]Patent: WO2009/102318,2009,A1
[7]Patent: US2010/249190,2010,A1

22
[ 53934-78-4 ]
[ 1007879-93-7 ]

Reference： [1]Patent: WO2011/60000,2011,A1
[2]Patent: WO2011/59850,2011,A1
[3]Patent: WO2012/18325,2012,A1
[4]Patent: EP2328865,2017,B1
[5]Patent: US2008/44379,2008,A1
[6]Patent: US2010/249190,2010,A1

23
[ 53934-78-4 ]
[ 714976-58-6 ]

Reference： [1]Patent: WO2011/60000,2011,A1
[2]Patent: US2008/44380,2008,A1

24
[ 53934-78-4 ]
[ 1307303-67-8 ]

Reference： [1]Patent: WO2011/60000,2011,A1

25
[ 540-88-5 ]
[ 875-74-1 ]
[ 53934-78-4 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 182 - 185
[2]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4854 - 4858

26
[ 53934-78-4 ]
[ 590-86-3 ]
C₂₁H₃₁F₂NO₄ [ No CAS ]
[ 1347655-19-9 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 182 - 185

27
[ 53934-78-4 ]
[ 590-86-3 ]
[ 1347655-35-9 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 182 - 185

28
[ 53934-78-4 ]
[ 98-59-9 ]
tert-butyl (2R)-(tosylamino)(phenyl)acetate [ No CAS ]

Reference： [1]Synthesis,2012,vol. 44,p. 1584 - 1590

29
[ 53934-78-4 ]
[ 98-59-9 ]
[ 1384465-77-3 ]

Reference： [1]Synthesis,2012,vol. 44,p. 1584 - 1590

30
[ 53934-78-4 ]
[ 1387577-05-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4854 - 4858

31
[ 53934-78-4 ]
C₁₄H₁₃NO₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4854 - 4858

32
[ 53934-78-4 ]
[ 106-96-7 ]
[ 1387577-07-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4854 - 4858

33
[ 53934-78-4 ]
[ 17350-17-3 ]
[ 1528767-55-6 ]

Yield	Reaction Conditions	Operation in experiment
92%	With benzotriazol-1-ol; triethylamine; dicyclohexyl-carbodiimide; In dichloromethane; at 0 - 20℃; for 19h;	General procedure: To a stirred solution of dipeptide 10 (1.29 g, 3.26 mmol) in dry CH2Cl2 (20 mL) at 0 C, 1-hydroxybenzotriazole (HOBt) (0.44 g, 3.26 mmol), H-Asp(OtBu)-OtBu (0.92 g, 3.26 mmol), Et3N (0.70 mL, 5.00 mmol), and dicyclohexyl carbodiimide (DCC) (0.72 g, 3.26 mmol) were added consecutively. The reaction mixture was left stirring at 0 C for 1 h and then warmed to rt and left stirring for 18 h. The solvents were evaporated under reduced pressure and the crude product was dissolved in EtOAc (30 mL). After filtration, the organic layer was washed with aqueous H2SO4 (5%, 20 mL), H2O (20 mL), aqueous NaHCO3 (5%, 20 mL), and brine (20 mL). After evaporation of the solvent, the crude ester was purified using column chromatography eluting with Pet. Ether/EtOAc (30:70

Reference： [1]Tetrahedron,2014,vol. 70,p. 608 - 615

34
[ 53934-78-4 ]
[ 17350-17-3 ]
[ 1528767-61-4 ]

Reference： [1]Tetrahedron,2014,vol. 70,p. 608 - 615

35
[ 63555-50-0 ]
[ 53934-78-4 ]
[ 1611455-10-7 ]

Yield	Reaction Conditions	Operation in experiment
43%	With triethylamine; In tetrahydrofuran; at 20℃; for 0.5h;	A stirred solution of tert-butyl-2-amino-2-phenylacetate (1.34 g, 6.45 mmol) and methyl 3-(chlorosulfonyl)benzoate (1.53 g, 6.51 mmol) in tetrahydrofuran (15 mL) was added with triethylamine (0.90 mL, 6.45 mmol) in one portion at ambient temperature. The reaction mixture was stirred for 30 minutes, after which time, the reaction mixture was concentrated under reduced pressure and partitioned between ethyl acetate (30 mL)and 10% citric acid solution (10 mL). The resulting organic phases were dried over magnesium sulfate and concentrated under reduced pressure to yield a crude solid. The solid was triturated in diethyl ether (5 mL) and cold methanol (5 mL) to yield the title compound as a white solid (1.13 g, 43%).?H NMR (400 MHz, CDC13): oe 8.32 (t, J = 1.9 Hz, 1 H), 8.12 (dt, J = 7.9, 1.5 Hz,1 H), 7.86 (ddd, J = 7.9, 1.9, 1.2 Hz, 1 H), 7.44 (t, J = 7.9 Hz, 1 H), 7.22-7.13 (m, 5 H),5.79 (d, J = 7.6 Hz, 1 H), 5.00 (d, J = 7.7 Hz, 1 H), 3.94 (s, 3 H), 1.26 (s, 9 H). LCMS (Method 2): [M-H] = 404 at 4.12 mm.
43%	With triethylamine; In tetrahydrofuran; at 20℃; for 0.5h;	Methyl 3-[(2-tert-butoxy-2-oxo-1-phenylethyl)sulfamoyl]benzoate (I-22) To a stirred solution of tert-butyl-2-amino-2-phenylacetate (1.34 g, 6.45 mmol) and methyl 3-(chlorosulfonyl)benzoate (1.53 g, 6.51 mmol) in tetrahydrofuran (15 mL) was added triethylamine (0.90 mL, 6.45 mmol) in one portion at ambient temperature. The reaction mixture was stirred for 30 minutes, after which time, the reaction mixture was concentrated under reduced pressure and partitioned between ethyl acetate (30 mL) and 10% citric acid solution (10 mL). The resulting organic phases were dried over magnesium sulfate and concentrated under reduced pressure to yield a crude solid. The solid was triturated in diethyl ether (5 mL) and cold methanol (5 mL) to yield the title compound as a white solid (1.13 g, 43%). 1H NMR (400 MHz, CDCl3): delta 8.32 (t, J=1.9 Hz, 1H), 8.12 (dt, J=7.9, 1.5 Hz, 1H), 7.86 (ddd, J=7.9, 1.9, 1.2 Hz, 1H), 7.44 (t, J=7.9 Hz, 1H), 7.22-7.13 (m, 5H), 5.79 (d, J=7.6 Hz, 1H), 5.00 (d, J=7.7 Hz, 1H), 3.94 (s, 3H), 1.26 (s, 9H). LCMS (Method 2): [M-H]=404 at 4.12 min.

Reference： [1]Patent: WO2014/86849,2014,A1 .Location in patent: Page/Page column 80
[2]Patent: US2014/155428,2014,A1 .Location in patent: Paragraph 0463 - 0465

36
[ 4747-71-1 ]
[ 53934-78-4 ]
[ 1007880-00-3 ]

Reference： [1]Patent: EP2328865,2017,B1
[2]Patent: US2008/44380,2008,A1
[3]Patent: US2010/249190,2010,A1

37
[ 53934-78-4 ]
1,1-dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N-((S)-1-{N-[(S)-2-(t-butoxy)-1-(t-butoxycarbonyl)ethyl]carbamoyl}propyl)carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine [ No CAS ]