4,4,4-trifluoro-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Following General Procedure D above using 1-(S)-[L-alaninyl]-amino-3-methyl-4,5,6,7-tetrahydro-2H-3-benzazepin-2-one hydrochloride (Example 7-30, below) and 2-(N-Boc-amino)-4,4,4-trifluorobutyric acid (Oakwood), the protected intermediate was prepared. The Boc-group was removed using 5.0 M HCl in dioxane and the resulting free-base purified by flash chromatography CHCl3/MeOH (97.3) yielding the title compounds. the protected intermediate was prepared The Boc-group was removed the resulting free-base purified by flash chromatography CHCl3/MeOH (97.3)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Following General Procedure D above using 1-(S)-[L-alaninyl]-amino-3-methyl-4,5,6,7-tetrahydro-2H-3-benzazepin-2-one hydrochloride (Example 7-30, below) and 2-(N-Boc-amino)-4,4,4-trifluorobutyric acid (Oakwood), the protected intermediate was prepared. The Boc-group was removed using 5.0 M HCl in dioxane and the resulting free-base purified by flash chromatography CHCl3/MeOH (97.3) yielding the title compounds. the protected intermediate was prepared The Boc-group was removed the resulting free-base purified by flash chromatography CHCl3/MeOH (97.3)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 421 mg (1.64 mmol) of 2-(tert-butoxycarbonylamino)-4,4,4-trifluorobutanoic acid were suspended in a mixture of N,N-dimethylformamide (5 mL) and dichloromethane (5 mL) and HATU (624 mg, 1.64 mmol) and DIEA (286 μl, 1.64 mmol) were added. The resulting suspension was stirred at room temperature for 2 hours and then 1-amino-N-phenyl-1H-pyrrole-2-carboxamide (300 mg, 1.49 mmol) was added. The resulting solution was stirred at room temperature overnight and the dichloromethane was removed in vacuum. 25 mL of water were added to the remaining solution and, after vigorous stirring, the solid that formed was filtered and washed with water. 582 mg (89% yield) of the title compound were obtained as a white solid. were added The resulting solution was stirred at room temperature overnight the dichloromethane was removed in vacuum 25 mL of water were added to the remaining solution after vigorous stirring, the solid that formed was filtered washed with water

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 421 mg (1.64 mmol) of 2-(tert-butoxycarbonylamino)-4,4,4-trifluorobutanoic acid were suspended in a mixture of N,N-dimethylformamide (5 mL) and dichloromethane (5 mL) and HATU (624 mg, 1.64 mmol) and DIEA (286 μl, 1.64 mmol) were added. The resulting suspension was stirred at room temperature for 2 hours and then 1-amino-N-phenyl-1H-pyrrole-2-carboxamide (300 mg, 1.49 mmol) was added. The resulting solution was stirred at room temperature overnight and the dichloromethane was removed in vacuum. 25 mL of water were added to the remaining solution and, after vigorous stirring, the solid that formed was filtered and washed with water. 582 mg (89% yield) of the title compound were obtained as a white solid. were added The resulting solution was stirred at room temperature overnight the dichloromethane was removed in vacuum 25 mL of water were added to the remaining solution after vigorous stirring, the solid that formed was filtered washed with water

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Following General Procedure D above using 1-(S)-[L-alaninyl]-amino-3-methyl-4,5,6,7-tetrahydro-2H-3-benzazepin-2-one hydrochloride (Example 7-30, below) and 2-(N-Boc-amino)-4,4,4-trifluorobutyric acid (Oakwood), the protected intermediate was prepared. The Boc-group was removed using 5.0 M HCl in dioxane and the resulting free-base purified by flash chromatography CHCl3/MeOH (97.3) yielding the title compounds. the protected intermediate was prepared The Boc-group was removed the resulting free-base purified by flash chromatography CHCl3/MeOH (97.3)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Following General Procedure D above using 1-(S)-[L-alaninyl]-amino-3-methyl-4,5,6,7-tetrahydro-2H-3-benzazepin-2-one hydrochloride (Example 7-30, below) and 2-(N-Boc-amino)-4,4,4-trifluorobutyric acid (Oakwood), the protected intermediate was prepared. The Boc-group was removed using 5.0 M HCl in dioxane and the resulting free-base purified by flash chromatography CHCl3/MeOH (97.3) yielding the title compounds. the protected intermediate was prepared The Boc-group was removed the resulting free-base purified by flash chromatography CHCl3/MeOH (97.3)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-(tert-butoxycarbonylamino)-4,4,4-trifluorobutanoic acid (370 mg, 1.43 mmol) and HOBt hydrate (264 mg, 1.72 mmol) in DMF (5 mL), EDC (332 mg, 1.72 mmol) was added. After being stirred at room temperature for 1 h, conc. NH4OH (14 N, 0.600 mL, 8.40 mmol) was added. The mixture was stirred for 18 h. Water and EtOAc were added. The organic phase was washed with 5% NaHCO3, dried over Na2SO4, concentrated in vacuo to give tert-butyl 1-amino-4,4,4-trifluoro-1-oxobutan-2-ylcarbamate as a solid. The mixture was stirred for 18 h The organic phase was washed with 5% NaHCO3 dried over Na2SO4 concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-(tert-butoxycarbonylamino)-4,4,4-trifluorobutanoic acid (370 mg, 1.43 mmol) and HOBt hydrate (264 mg, 1.72 mmol) in DMF (5 mL), EDC (332 mg, 1.72 mmol) was added. After being stirred at room temperature for 1 h, conc. NH4OH (14 N, 0.600 mL, 8.40 mmol) was added. The mixture was stirred for 18 h. Water and EtOAc were added. The organic phase was washed with 5% NaHCO3, dried over Na2SO4, concentrated in vacuo to give tert-butyl 1-amino-4,4,4-trifluoro-1-oxobutan-2-ylcarbamate as a solid. The mixture was stirred for 18 h The organic phase was washed with 5% NaHCO3 dried over Na2SO4 concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Following General Procedure D above using 1-(S)-[L-alaninyl]-amino-3-methyl-4,5,6,7-tetrahydro-2H-3-benzazepin-2-one hydrochloride (Example 7-30, below) and 2-(N-Boc-amino)-4,4,4-trifluorobutyric acid (Oakwood), the protected intermediate was prepared. The Boc-group was removed using 5.0 M HCl in dioxane and the resulting free-base purified by flash chromatography CHCl3/MeOH (97.3) yielding the title compounds. the protected intermediate was prepared The Boc-group was removed the resulting free-base purified by flash chromatography CHCl3/MeOH (97.3)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 421 mg (1.64 mmol) of 2-(tert-butoxycarbonylamino)-4,4,4-trifluorobutanoic acid were suspended in a mixture of N,N-dimethylformamide (5 mL) and dichloromethane (5 mL) and HATU (624 mg, 1.64 mmol) and DIEA (286 μl, 1.64 mmol) were added. The resulting suspension was stirred at room temperature for 2 hours and then 1-amino-N-phenyl-1H-pyrrole-2-carboxamide (300 mg, 1.49 mmol) was added. The resulting solution was stirred at room temperature overnight and the dichloromethane was removed in vacuum. 25 mL of water were added to the remaining solution and, after vigorous stirring, the solid that formed was filtered and washed with water. 582 mg (89% yield) of the title compound were obtained as a white solid. were added The resulting solution was stirred at room temperature overnight the dichloromethane was removed in vacuum 25 mL of water were added to the remaining solution after vigorous stirring, the solid that formed was filtered washed with water

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Following General Procedure D above using 1-(S)-[L-alaninyl]-amino-3-methyl-4,5,6,7-tetrahydro-2H-3-benzazepin-2-one hydrochloride (Example 7-30, below) and 2-(N-Boc-amino)-4,4,4-trifluorobutyric acid (Oakwood), the protected intermediate was prepared. The Boc-group was removed using 5.0 M HCl in dioxane and the resulting free-base purified by flash chromatography CHCl3/MeOH (97.3) yielding the title compounds. the protected intermediate was prepared The Boc-group was removed the resulting free-base purified by flash chromatography CHCl3/MeOH (97.3)