Hydrochloric Acid → (1-{3-Acetyl-5-[2-(4-bromo-phenyl)-2-oxo-ethylcarbamoyl]-imidazolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

HRID 71805

Reaction equation

HRID 71805 reaction equation
CO[C:3]([CH:5]1[CH2:9][N:8]([C:10](=[O:12])[CH3:11])[CH2:7][N:6]1[C:13](=[O:23])[CH:14]([NH:18][C:19]([O:21][CH3:22])=[O:20])[CH:15]([CH3:17])[CH3:16])=[O:4].[Li+].[OH-].Cl.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl.[NH2:61][CH2:62][C:63]([C:65]1[CH:70]=[CH:69][C:68]([Br:71])=[CH:67][CH:66]=1)=[O:64]>C1COCC1.CO>[CH3:22][O:21][C:19](=[O:20])[NH:18][CH:14]([C:13]([N:6]1[CH:5]([C:3](=[O:4])[NH:61][CH2:62][C:63]([C:65]2[CH:70]=[CH:69][C:68]([Br:71])=[CH:67][CH:66]=2)=[O:64])[CH2:9][N:8]([C:10](=[O:12])[CH3:11])[CH2:7]1)=[O:23])[CH:15]([CH3:16])[CH3:17]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 27982162-Amino-1-(4-bromophenyl)ethan-1-one hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 666209721-Acetyl-3-(2-methoxycarbonylamino-3-methyl-butyryl)-imidazolidine-4-carboxylic acid methyl ester

Product 1

HCID 66620312(1-{3-Acetyl-5-[2-(4-bromo-phenyl)-2-oxo-ethylcarbamoyl]-imidazolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl esterYield 47.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-Acetyl-3-(2-methoxycarbonylamino-3-methyl-butyryl)-imidazolidine-4-carboxylic acid methyl ester (273 mg, 0.829 mmol) was dissolved in THF (1.8 mL) and MeOH (1.2 mL). An aqueous solution of LiOH (34.8 mg, 0.829 mmol) was added and stirring at room temperature was continued. After the hydrolysis was complete, the reaction was neutralized with aqueous HCl (0.83 mL, 1M). The organic solvents were removed in vacuo and the aqueous suspension was frozen and lyophilized. The crude material was used in the next step without further purification. The crude material was dissolved in DMF (3 mL) and HATU (315 mg, 0.829 mmol) and DIEA (106 mg, 0.829 mmol) were added. The reaction was stirred at room temperature for five minutes, after which the amino-(4′bromo) acetophenone hydrochloride salt (207 mg, 0.829 mmol) was added. Stirring at room temperature was continued. After 120 minutes, all volatiles were removed in vacuo and the crude material was dissolved in DCM. The organic layer was washed with aqueous HCl (0.5 M), aqueous lithium chloride solution (5%), brine and was dried over sodium sulfate. Filtration and evaporation of solvents yielded crude product which was purified via silica gel chromatography (eluent EtOAc/hexanes) to yield the product (1-{3-Acetyl-5-[2-(4-bromo-phenyl)-2-oxo-ethylcarbamoyl]-imidazolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (203 mg, 0.397 mmol): LCMS-ESI+: calc'd for C21H27BrN4O6: 511.4 (M+). Found: 511.3/513.2 (M+H+).

Workup

  1. customThe organic solvents were removed in vacuo
  2. temperaturethe aqueous suspension was frozen
  3. customThe crude material was used in the next step without further purification
  4. dissolutionThe crude material was dissolved in DMF (3 mL)
  5. stirringThe reaction was stirred at room temperature for five minutes
  6. stirringStirring at room temperature
  7. customall volatiles were removed in vacuo
  8. dissolutionthe crude material was dissolved in DCM
  9. washThe organic layer was washed with aqueous HCl (0.5 M), aqueous lithium chloride solution (5%), brine
  10. dry with materialwas dried over sodium sulfate
  11. filtrationFiltration and evaporation of solvents
  12. customyielded crude product which
  13. customwas purified via silica gel chromatography (eluent EtOAc/hexanes)

Sources & evidence

ORD record
ord-b82b2bb6ff674c5eb0383c26cbb35eb9
Source dataset
uspto-grants-2014_09
Patent number
US08822430B2

Linked notes

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