反応 #10165

反応方程式

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

溶媒

DCM

DCM

反応条件

後処理

1. 1
   workup.STIRRINGThe reaction mixture was stirred at ambient temperature under N2 for 2 hours
2. 2
   濃縮concentrated under vacuum
3. 3
   その他partitioned between water and ethyl acetate
4. 4
   抽出The organic extract
5. 5
   洗浄was washed with brine
6. 6
   乾燥dried over anhydrous magnesium sulfate
7. 7
   ろ過filtered
8. 8
   濃縮concentrated under vacuum
9. 9
   洗浄eluted with 40% MeOH in CHCl3
10. 10
    その他Collection and concentration of appropriate fractions

実験手順

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.

出典