Diisopropylethylamine → 3-Fluoro-4'-{(1r)-1-[({1-[(3,3,3-trifluoropropanoyl)amino]cyclopropyl}carbonyl)-amino]ethyl}-1,1'-biphenyl-2-carboxylic acid

HRID 896711

Reaktionsgleichung

Reaktionsgleichung von HRID 896711
[F:1][C:2]([F:8])([F:7])[CH2:3][C:4](O)=[O:5].Cl.C(N=C=NCCCN(C)C)C.ON1C2N=CC=CC=2N=N1.[NH2:31][C:32]1([C:35]([NH:37][C@@H:38]([C:40]2[CH:45]=[CH:44][C:43]([C:46]3[C:47]([C:53]([OH:55])=[O:54])=[C:48]([F:52])[CH:49]=[CH:50][CH:51]=3)=[CH:42][CH:41]=2)[CH3:39])=[O:36])[CH2:34][CH2:33]1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[F:52][C:48]1[CH:49]=[CH:50][CH:51]=[C:46]([C:43]2[CH:42]=[CH:41][C:40]([C@H:38]([NH:37][C:35]([C:32]3([NH:31][C:4](=[O:5])[CH2:3][C:2]([F:8])([F:7])[F:1])[CH2:34][CH2:33]3)=[O:36])[CH3:39])=[CH:45][CH:44]=2)[C:47]=1[C:53]([OH:55])=[O:54]

Komponenten

7

Edukt 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27779723,3,3-Trifluoropropionic acidHCID 695631874'-((1R)-1-{[(1-aminocyclopropyl)carbonyl]amino}ethyl)-3-fluoro-1,1'-biphenyl-2-carboxylic acid

Produkt 1

HCID 695640683-Fluoro-4'-{(1r)-1-[({1-[(3,3,3-trifluoropropanoyl)amino]cyclopropyl}carbonyl)-amino]ethyl}-1,1'-biphenyl-2-carboxylic acid

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

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.

Aufarbeitung

  1. stirringThe reaction mixture was stirred at ambient temperature under N2 for 2 hours
  2. concentrationconcentrated under vacuum
  3. custompartitioned between water and ethyl acetate
  4. extractionThe organic extract
  5. washwas washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. washeluted with 40% MeOH in CHCl3
  10. customCollection and concentration of appropriate fractions

Quellen und Nachweise

ORD-Eintrag
ord-5ea53a1ca3c54a6aa2efc86d9d305ae4
Quelldatensatz
uspto-grants-2005_07
Patentnummer
US06919343B2

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