tert-butyl 3-(3-aminophenyl)propanoate

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

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

Procedure: 5-(2-Adamantan-1-yl-ethyl)-2-o-tolyl-1H-imidazole-4-carboxylic acid (Example 93) (364 mg, 1.00 mmol) was reacted with 3-(3-amino-phenyl)-propionic acid tert-butyl ester (243 mg, 1.10 mmol) according to the procedure of Example 70, step c to afford the product as a colourless foam (359 mg, 63%). 1H NMR (300 MHz, CDCl3) 9.14 (1H, br s), 9.07 (1H, br s), 7.59-7.51 (3H, m), 7.35-7.22 (4H, m), 6.94 (1H, d), 3.16 (2H, m), 2.92 (2H, m), 2.60 (3H, s), 2.56 (2H, m), 1.99 (3H, s), 1.76-1.44 (23H, m).

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

Procedure: 5-(2-Adamantan-1-yl-ethyl)-2-o-tolyl-1H-imidazole-4-carboxylic acid (Example 93) (364 mg, 1.00 mmol) was reacted with 3-(3-amino-phenyl)-propionic acid tert-butyl ester (243 mg, 1.10 mmol) according to the procedure of Example 70, step c to afford the product as a colourless foam (359 mg, 63%). 1H NMR (300 MHz, CDCl3) 9.14 (1H, br s), 9.07 (1H, br s), 7.59-7.51 (3H, m), 7.35-7.22 (4H, m), 6.94 (1H, d), 3.16 (2H, m), 2.92 (2H, m), 2.60 (3H, s), 2.56 (2H, m), 1.99 (3H, s), 1.76-1.44 (23H, m).

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

Procedure: 215.3 mg (0.89 mmol) of tert-butyl 3-(3-aminophenyl)propanoate were added to a solution of 280.0 mg (0.71 mmol) of 4,4,4-trifluoro-2-{4-[(4-fluoro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-3-methylbutanoic acid and 114.8 mg (0.85 mmol) of 1-hydroxy-1H-benzotriazole hydrate in 1.4 ml of DMF. At 0° C., 308 μl (1.77 mmol) of DIEA and then, a little at a time, 296.2 mg (0.78 mmol) of HATU were added to the resulting mixture. The reaction mixture was then slowly warmed to RT and subsequently stirred at RT for 2.5 h. The mixture was added to water and extracted three times with ethyl acetate. The combined organic phases were dried over magnesium sulfate and concentrated under reduced pressure. The crude product was purified by preparative RP-HPLC (mobile phase: acetonitrile/water gradient). This gave 333 mg (78.6% of theory) of the title compound. extracted three times with ethyl acetate The combined organic phases were dried over magnesium sulfate concentrated under reduced pressure The crude product was purified by preparative RP-HPLC (mobile phase: acetonitrile/water gradient)

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

Procedure: 215.3 mg (0.89 mmol) of tert-butyl 3-(3-aminophenyl)propanoate were added to a solution of 280.0 mg (0.71 mmol) of 4,4,4-trifluoro-2-{4-[(4-fluoro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-3-methylbutanoic acid and 114.8 mg (0.85 mmol) of 1-hydroxy-1H-benzotriazole hydrate in 1.4 ml of DMF. At 0° C., 308 μl (1.77 mmol) of DIEA and then, a little at a time, 296.2 mg (0.78 mmol) of HATU were added to the resulting mixture. The reaction mixture was then slowly warmed to RT and subsequently stirred at RT for 2.5 h. The mixture was added to water and extracted three times with ethyl acetate. The combined organic phases were dried over magnesium sulfate and concentrated under reduced pressure. The crude product was purified by preparative RP-HPLC (mobile phase: acetonitrile/water gradient). This gave 333 mg (78.6% of theory) of the title compound. extracted three times with ethyl acetate The combined organic phases were dried over magnesium sulfate concentrated under reduced pressure The crude product was purified by preparative RP-HPLC (mobile phase: acetonitrile/water gradient)

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

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

Procedure: 5-(2-Adamantan-1-yl-ethyl)-2-o-tolyl-1H-imidazole-4-carboxylic acid (Example 93) (364 mg, 1.00 mmol) was reacted with 3-(3-amino-phenyl)-propionic acid tert-butyl ester (243 mg, 1.10 mmol) according to the procedure of Example 70, step c to afford the product as a colourless foam (359 mg, 63%). 1H NMR (300 MHz, CDCl3) 9.14 (1H, br s), 9.07 (1H, br s), 7.59-7.51 (3H, m), 7.35-7.22 (4H, m), 6.94 (1H, d), 3.16 (2H, m), 2.92 (2H, m), 2.60 (3H, s), 2.56 (2H, m), 1.99 (3H, s), 1.76-1.44 (23H, m).

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

Procedure: 215.3 mg (0.89 mmol) of tert-butyl 3-(3-aminophenyl)propanoate were added to a solution of 280.0 mg (0.71 mmol) of 4,4,4-trifluoro-2-{4-[(4-fluoro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-3-methylbutanoic acid and 114.8 mg (0.85 mmol) of 1-hydroxy-1H-benzotriazole hydrate in 1.4 ml of DMF. At 0° C., 308 μl (1.77 mmol) of DIEA and then, a little at a time, 296.2 mg (0.78 mmol) of HATU were added to the resulting mixture. The reaction mixture was then slowly warmed to RT and subsequently stirred at RT for 2.5 h. The mixture was added to water and extracted three times with ethyl acetate. The combined organic phases were dried over magnesium sulfate and concentrated under reduced pressure. The crude product was purified by preparative RP-HPLC (mobile phase: acetonitrile/water gradient). This gave 333 mg (78.6% of theory) of the title compound. extracted three times with ethyl acetate The combined organic phases were dried over magnesium sulfate concentrated under reduced pressure The crude product was purified by preparative RP-HPLC (mobile phase: acetonitrile/water gradient)