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ノート

反応式

HRID 10068 の反応式
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

参加物

4

反応物 1

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 6422Trifluoroacetic acid溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-62a465eb4b2d4de2a03a1d9082e584b5
出典データセット
uspto-grants-2006_08
特許番号
US07091380B2

反応ノート

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