(3S)-4-[4-(2-acetyl-1-methyl-1H-imidazol-4-yl)phenyl]-3-[([3-chloro-4-[(1-methylethyl)oxy]phenyl}carbonyl)amino]butyl dimethyl phosphate → (3S)-4-[4-(2-acetyl-1-methyl-1H-imidazol-4-yl)phenyl]-3-[({3-chloro-4-[(1-methylethyl)oxy]phenyl}carbonyl)amino]butyl dihydrogen phosphate

HRID 1621234

Reaktionsgleichung

Reaktionsgleichung von HRID 1621234
[P:1]([O:39]C)([O:37]C)([O:3][CH2:4][CH2:5][C@@H:6]([NH:23][C:24]([C:26]1[CH:31]=[CH:30][C:29]([O:32][CH:33]([CH3:35])[CH3:34])=[C:28]([Cl:36])[CH:27]=1)=[O:25])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:15]=[C:16]([C:20](=[O:22])[CH3:21])[N:17]([CH3:19])[CH:18]=2)=[CH:10][CH:9]=1)=[O:2]>Br.CC(O)=O>[P:1]([OH:37])([OH:39])([O:3][CH2:4][CH2:5][C@@H:6]([NH:23][C:24]([C:26]1[CH:31]=[CH:30][C:29]([O:32][CH:33]([CH3:35])[CH3:34])=[C:28]([Cl:36])[CH:27]=1)=[O:25])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:15]=[C:16]([C:20](=[O:22])[CH3:21])[N:17]([CH3:19])[CH:18]=2)=[CH:10][CH:9]=1)=[O:2]

Komponenten

4

Edukt 1

HCID 57594157(3S)-4-[4-(2-acetyl-1-methyl-1H-imidazol-4-yl)phenyl]-3-[([3-chloro-4-[(1-methylethyl)oxy]phenyl}carbonyl)amino]butyl dimethyl phosphate

Produkt 1

HCID 16723062(3S)-4-[4-(2-acetyl-1-methyl-1H-imidazol-4-yl)phenyl]-3-[({3-chloro-4-[(1-methylethyl)oxy]phenyl}carbonyl)amino]butyl dihydrogen phosphateAusbeute 19 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittelHCID 260Hydrogen BromideLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

A yellow solution of (3S)-4-[4-(2-acetyl-1-methyl-1H-imidazol-4-yl)phenyl]-3-[({3-chloro-4-[(1-methylethyl)oxy]phenyl}carbonyl)amino]butyl dimethyl phosphate (475 mg, 0.804 mmol) in 30% HBr in AcOH was placed in a pre-heated (60° C.) bath for 10 min, then immediately allowed to cool to rt. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in DMSO (6 mL), filtered and purified by Gilson reverse phase HPLC (MeCN/H2O with 0.1% TFA). The MeCN of the clean fractions was removed under reduced pressure and the remaining aqueous solution was frozen and lyophilized overnight to give 84 mg (19%) of the title compound as a yellow powder. LC/MS (ES) m/e 564.2 (M+H)+.

Aufarbeitung

  1. temperatureto cool to rt
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. dissolutionthe residue was dissolved in DMSO (6 mL)
  4. filtrationfiltered
  5. custompurified by Gilson reverse phase HPLC (MeCN/H2O with 0.1% TFA)
  6. customThe MeCN of the clean fractions was removed under reduced pressure
  7. temperaturethe remaining aqueous solution was frozen

Quellen und Nachweise

ORD-Eintrag
ord-81135ff521574ba0a088adc76dfe67c4
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08772507B2

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