(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 222903

Reaction equation

HRID 222903 reaction equation
[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]

Participants

4

Reactant 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

Product 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 phosphateYield 19%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 260Hydrogen BromideSolvent

Conditions

Temperature
60 °C

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-7ab5904eb11042dcbd6978f6a3eefed4
Source dataset
uspto-grants-2012_06
Patent number
US08207340B2

Linked notes

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