تفاعل #10165

معادلة التفاعل

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

المذيبات

DCM

DCM

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGThe reaction mixture was stirred at ambient temperature under N2 for 2 hours
2. 2
   تركيزconcentrated under vacuum
3. 3
   أخرىpartitioned between water and ethyl acetate
4. 4
   استخلاصThe organic extract
5. 5
   غسيلwas washed with brine
6. 6
   تجفيفdried over anhydrous magnesium sulfate
7. 7
   ترشيحfiltered
8. 8
   تركيزconcentrated under vacuum
9. 9
   غسيلeluted with 40% MeOH in CHCl3
10. 10
    أخرىCollection and concentration of appropriate fractions

الإجراء التجريبي

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.

المصدر