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 896710노트

반응식

HRID 896710 반응식
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

참가 물질

4

반응물 1

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

생성물 1

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

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 6422Trifluoroacetic acid용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-9cca5f23db0c4cd58968c71e5646a9ee
출처 데이터셋
uspto-grants-2005_07
특허 번호
US06919343B2

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