Реакция #10165

Уравнение реакции

trifluoropropionic acid

1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride

1-hydroxy-7-azabenzotriazole

4′-((1R)-1-{[(1-aminocyclopropyl)carbonyl]amino}ethyl)-3-fluoro-1,1′-biphenyl-2-carboxylic acid

N,N-diisopropylethylamine

→

3-fluoro-4′-{(1R)-1-[({1-[(3,3,3-trifluoropropanoyl)amino]cyclopropyl}carbonyl)-amino]ethyl}-1,1′-biphenyl-2-carboxylic acid

Растворители

DCM

DCM

Условия реакции

Обработка

1. 1
   workup.STIRRINGThe reaction mixture was stirred at ambient temperature under N2 for 2 hours
2. 2
   Концентрированиеconcentrated under vacuum
3. 3
   Другоеpartitioned between water and ethyl acetate
4. 4
   ЭкстракцияThe organic extract
5. 5
   Промывкаwas washed with brine
6. 6
   Сушкаdried over anhydrous magnesium sulfate
7. 7
   Фильтрацияfiltered
8. 8
   Концентрированиеconcentrated under vacuum
9. 9
   Промывкаeluted with 40% MeOH in CHCl3
10. 10
    ДругоеCollection and concentration of appropriate fractions

Методика

To a solution of trifluoropropionic acid (128 mg, 1.0 mmol) in DCM (1 mL), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (229 mg, 1.2 mmol) and 1-hydroxy-7-azabenzotriazole (136 mg, 1.0 mmol) were added. The resulting solution was stirred at room temperature for 20 minutes, then 4′-((1R)-1-{[(1-aminocyclopropyl)carbonyl]amino}ethyl)-3-fluoro-1,1′-biphenyl-2-carboxylic acid (171 mg, 0.5 mmol) in 1 mL DCM was added, followed by N,N-diisopropylethylamine until pH=10 was achieved. The reaction mixture was stirred at ambient temperature under N2 for 2 hours, concentrated under vacuum and then partitioned between water and ethyl acetate. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluted with 40% MeOH in CHCl3. Collection and concentration of appropriate fractions provided 3-fluoro-4′-{(1R)-1-[({1-[(3,3,3-trifluoropropanoyl)amino]cyclopropyl}carbonyl)-amino]ethyl}-1,1′-biphenyl-2-carboxylic acid as a white powder.

Источник