methyl 4'-{(1R)-1-[({1-[(tert-butoxycarbonyl)amino]-cyclopropyl}carbonyl)amino]ethyl}-3-fluoro-1,1'-biphenyl-2-carboxylate → 4'-((1R)-1-{[(1-aminocyclopropyl)carbonyl]amino}ethyl)-3-fluoro-1,1'-biphenyl-2-carboxylic acid

HRID 10068

Reaktionsgleichung

Reaktionsgleichung von HRID 10068
C(OC([NH:8][C:9]1([C:12]([NH:14][C@@H:15]([C:17]2[CH:22]=[CH:21][C:20]([C:23]3[C:24]([C:30]([O:32]C)=[O:31])=[C:25]([F:29])[CH:26]=[CH:27][CH:28]=3)=[CH:19][CH:18]=2)[CH3:16])=[O:13])[CH2:11][CH2:10]1)=O)(C)(C)C>C(Cl)Cl.C(O)(C(F)(F)F)=O>[NH2:8][C:9]1([C:12]([NH:14][C@@H:15]([C:17]2[CH:22]=[CH:21][C:20]([C:23]3[C:24]([C:30]([OH:32])=[O:31])=[C:25]([F:29])[CH:26]=[CH:27][CH:28]=3)=[CH:19][CH:18]=2)[CH3:16])=[O:13])[CH2:10][CH2:11]1

Komponenten

4

Edukt 1

HCID 69563684methyl 4'-{(1R)-1-[({1-[(tert-butoxycarbonyl)amino]-cyclopropyl}carbonyl)amino]ethyl}-3-fluoro-1,1'-biphenyl-2-carboxylate

Produkt 1

HCID 695631874'-((1R)-1-{[(1-aminocyclopropyl)carbonyl]amino}ethyl)-3-fluoro-1,1'-biphenyl-2-carboxylic acid

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 6422Trifluoroacetic acidLösungsmittel

Versuchsvorschrift

A solution of methyl 4′-{(1R)-1-[({1-[(tert-butoxycarbonyl)amino]-cyclopropyl}carbonyl)amino]ethyl}-3-fluoro-1,1′-biphenyl-2-carboxylate (466 mg, 1.0 mmol) in DCM (15 mL) and TFA (15 mL) was stirred under N2 for 20 minutes at ambient temperature, then the organic solvent was removed under vacuum. The residue was dissolved in MeOH (20 mL), 4N NaOH (10 mL) and water (10 mL). This mixture was heated at reflux for 4 hours and then neutralized with 6N HCl. Purification was achieved by preparative HPLC on a delta-pack C18 column, 300 Å, pore size 15 μM with 0.05% HCl acid-aqueous acetonitrile solvent systems using various linear gradients. Fractions containing product of 99% purity as measured by HPLC were combined and lyophilized to give 4′-((1R)-1-{[(1-aminocyclopropyl)-carbonyl]amino}ethyl)-3-fluoro-1,1′-biphenyl-2-carboxylic acid as a white solid.

Aufarbeitung

  1. customthe organic solvent was removed under vacuum
  2. dissolutionThe residue was dissolved in MeOH (20 mL)
  3. temperatureThis mixture was heated
  4. temperatureat reflux for 4 hours
  5. customPurification
  6. additionFractions containing product of 99% purity

Quellen und Nachweise

ORD-Eintrag
ord-62a465eb4b2d4de2a03a1d9082e584b5
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07091380B2

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