tert-butyl N-(2-amino-3-phenylpropyl)carbamate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: The title compound was prepared as a white solid according to the procedure of Example 24, except substituting 5-methyl-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic acid (168 mg, 0.5 mmol) [prepared according to Example 198] for 4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic acid, N-bromosuccinimide (88.5 mg, 0.5 mmol) for N-chlorosuccinimide and 1,1-dimethylethyl (2-amino-3-phenylpropyl)carbamate (71 mg, 0.3 mmol) [prepared according to the procedure of Preparation 1] for 1,1-dimethylethyl (3-amino-4-phenylbutyl)carbamate: LC-MS (ES) m/z 341 (M+H)+, 1H NMR (400 MHz, MeOD) δ ppm 2.39 (d, J=4.04 Hz, 3H) 3.42 (br. s., 1H) 3.55 (br. s., 1H) 3.75-3.78 (m, 3H) 5.45 (m, 1H) 7.37 (d, J=7.07 Hz, 1H) 7.40-7.46 (m, 2H) 7.49 (br. s., 2H) 7.59-7.68 (m, 1H) 7.80-7.88 (m, 1H). prepared

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

Procedure: To a solution of 5-chloro-4-methyl-2-thiophenecarboxylic acid (242 mg, 1.0 mmol) and diisopropylethyl amine (2.5 mL, 14.60 mmol) in DCM (50 mL) at 25° C. was added PyBrOP (2.5 g, 5.30 mmol) in one portion. After 30 min, 1,1-dimethylethyl (2-amino-3-phenylpropyl)carbamate (250 mg, 1.0 mmol) was added at one portion. After 2 h, the solution was concentrated and purified via column chromatography (silica, 10-40% EtOAc in Hexane) affording the title compound (460 mg, 97%) as a white solid: LC-MS (ES) m/z=474 (M+H)+. After 2 h the solution was concentrated purified via column chromatography (silica, 10-40% EtOAc in Hexane)

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

Procedure: To a solution of 5-chloro-4-methyl-2-thiophenecarboxylic acid (242 mg, 1.0 mmol) and diisopropylethyl amine (2.5 mL, 14.60 mmol) in DCM (50 mL) at 25° C. was added PyBrOP (2.5 g, 5.30 mmol) in one portion. After 30 min, 1,1-dimethylethyl (2-amino-3-phenylpropyl)carbamate (250 mg, 1.0 mmol) was added at one portion. After 2 h, the solution was concentrated and purified via column chromatography (silica, 10-40% EtOAc in Hexane) affording the title compound (460 mg, 97%) as a white solid: LC-MS (ES) m/z=474 (M+H)+. After 2 h the solution was concentrated purified via column chromatography (silica, 10-40% EtOAc in Hexane)

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

Procedure: To a 50 mL round-bottomed flask was added 4-bromo-1-methyl-1H-pyrrole-2-carboxylic acid (610 mg, 3.0 mmol), 1,1-dimethylethyl (2-amino-3-phenylpropyl)carbamate (748 mg, 2.99 mmol) [prepared according to the procedure of Preparation 2] and PyBrop (1.71 g, 3.67 mmol) in Chloroform (15 mL). DIEA (1.8 mL, 10.3 mmol) was added and the mixture stirred overnight at room temperature. The reaction mixture was adsorbed onto silica and purified via column chromatography (Hex/EtOAc) affording the title compound (335 mg, 26%): LC-MS (ES) m/z=438 (M+H)+. prepared purified via column chromatography (Hex/EtOAc)

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

Procedure: To a solution of 4,5-dibromo-2-furancarboxylic acid (2.81 g, 10.4 mmol), PyBrOP (5.6 g, 12.0 mmol) and diisopropylethyl amine (4.2 mL, 24.0 mmol) in DCM (70 mL) at 25° C. was added 1,1-dimethylethyl (2-amino-3-phenylpropyl)carbamate (2.0 g, 8.0 mmol). After 16 h, the solution was partitioned between H2O and washed with DCM. The combined organic fractions were dried (Na2SO4), concentrated and purified via column chromatography (silica, hexanes/EtOAc, 2:1) affording the title compound (4.3 g, 82%) as a white solid: LC-MS (ES) m/z=503 (M+H)+. the solution was partitioned between H2O washed with DCM The combined organic fractions were dried (Na2SO4) concentrated purified via column chromatography (silica, hexanes/EtOAc, 2:1)

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

Procedure: To a solution of 4,5-dibromo-2-furancarboxylic acid (2.81 g, 10.4 mmol), PyBrOP (5.6 g, 12.0 mmol) and diisopropylethyl amine (4.2 mL, 24.0 mmol) in DCM (70 mL) at 25° C. was added 1,1-dimethylethyl (2-amino-3-phenylpropyl)carbamate (2.0 g, 8.0 mmol). After 16 h, the solution was partitioned between H2O and washed with DCM. The combined organic fractions were dried (Na2SO4), concentrated and purified via column chromatography (silica, hexanes/EtOAc, 2:1) affording the title compound (4.3 g, 82%) as a white solid: LC-MS (ES) m/z=503 (M+H)+. the solution was partitioned between H2O washed with DCM The combined organic fractions were dried (Na2SO4) concentrated purified via column chromatography (silica, hexanes/EtOAc, 2:1)

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

Procedure: To a solution of 4,5-dibromo-2-furancarboxylic acid (2.81 g, 10.4 mmol), PyBrOP (5.6 g, 12.0 mmol) and diisopropylethyl amine (4.2 mL, 24.0 mmol) in DCM (70 mL) at 25° C. was added 1,1-dimethylethyl (2-amino-3-phenylpropyl)carbamate (2.0 g, 8.0 mmol). After 16 h, the solution was partitioned between H2O and washed with DCM. The combined organic fractions were dried (Na2SO4), concentrated and purified via column chromatography (silica, hexanes/EtOAc, 2:1) affording the title compound (4.3 g, 82%) as a white solid: LC-MS (ES) m/z=503 (M+H)+. the solution was partitioned between H2O washed with DCM The combined organic fractions were dried (Na2SO4) concentrated purified via column chromatography (silica, hexanes/EtOAc, 2:1)

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

Procedure: The title compound was prepared as a white solid according to the procedure of Example 24, except substituting 5-methyl-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic acid (168 mg, 0.5 mmol) [prepared according to Example 198] for 4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic acid, N-bromosuccinimide (88.5 mg, 0.5 mmol) for N-chlorosuccinimide and 1,1-dimethylethyl (2-amino-3-phenylpropyl)carbamate (71 mg, 0.3 mmol) [prepared according to the procedure of Preparation 1] for 1,1-dimethylethyl (3-amino-4-phenylbutyl)carbamate: LC-MS (ES) m/z 341 (M+H)+, 1H NMR (400 MHz, MeOD) δ ppm 2.39 (d, J=4.04 Hz, 3H) 3.42 (br. s., 1H) 3.55 (br. s., 1H) 3.75-3.78 (m, 3H) 5.45 (m, 1H) 7.37 (d, J=7.07 Hz, 1H) 7.40-7.46 (m, 2H) 7.49 (br. s., 2H) 7.59-7.68 (m, 1H) 7.80-7.88 (m, 1H). prepared

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

Procedure: To a solution of 5-chloro-4-methyl-2-thiophenecarboxylic acid (242 mg, 1.0 mmol) and diisopropylethyl amine (2.5 mL, 14.60 mmol) in DCM (50 mL) at 25° C. was added PyBrOP (2.5 g, 5.30 mmol) in one portion. After 30 min, 1,1-dimethylethyl (2-amino-3-phenylpropyl)carbamate (250 mg, 1.0 mmol) was added at one portion. After 2 h, the solution was concentrated and purified via column chromatography (silica, 10-40% EtOAc in Hexane) affording the title compound (460 mg, 97%) as a white solid: LC-MS (ES) m/z=474 (M+H)+. After 2 h the solution was concentrated purified via column chromatography (silica, 10-40% EtOAc in Hexane)