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

HRID 79765Notes

Reaction equation

HRID 79765 reaction equation
CO[C:3]([CH:5]1[CH2:9][N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:7][N:6]1[C:16](=[O:26])[CH:17]([NH:21][C:22]([O:24][CH3:25])=[O:23])[CH:18]([CH3:20])[CH3:19])=[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.[NH2:64][CH2:65][C:66]([C:68]1[CH:73]=[CH:72][C:71]([Br:74])=[CH:70][CH:69]=1)=[O:67]>C1COCC1.CO>[CH3:25][O:24][C:22](=[O:23])[NH:21][CH:17]([C:16]([N:6]1[CH:5]([C:3](=[O:4])[NH:64][CH2:65][C:66]([C:68]2[CH:73]=[CH:72][C:71]([Br:74])=[CH:70][CH:69]=2)=[O:67])[CH2:9][N:8]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:7]1)=[O:26])[CH:18]([CH3:20])[CH3:19]

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 666208283-(2-Methoxycarbonylamino-3-methyl-butyryl)-1-phenyl-imidazolidine-4-carboxylic acid methyl ester

Product 1

HCID 66621159(1-{5-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-3-phenyl-imidazolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl esterYield 124.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

3-(2-Methoxycarbonylamino-3-methyl-butyryl)-1-phenyl-imidazolidine-4-carboxylic acid methyl ester (51 mg, 0.14 mmol) was dissolved in THF (1.2 mL) and MeOH (0.8 mL). An aqueous solution of LiOH (6.0 mg, 0.14 mmol) was added and stirring at room temperature was continued. After the hydrolysis was complete, the reaction was neutralized with aqueous HCl (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 (1.5 mL) and HATU (54.3 mg, 0.14 mmol) and DIEA (36.9 mg, 0.28 mmol) were added. The reaction was stirred at room temperature for five minutes, after which the amino-(4′bromo) acetophenone hydrochloride salt (35.7 mg, 0.14 mmol) was added. Stirring at room temperature was continued. After 10 minutes, all volatiles were removed in vacuo and the crude material was purified via silica gel chromatography (eluent: EtOAc/hexanes) to yield the slightly impure product (95 mg): LCMS-ESI+: calc'd for C25H29BrN4O5: 545.4 (M+). Found: 545.2/547.4 (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 (1.5 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. customthe crude material was purified via silica gel chromatography (eluent: EtOAc/hexanes)

Sources & evidence

ORD record
ord-c2e8fbda4a324d0791a20425924a8551
Source dataset
uspto-grants-2014_09
Patent number
US08841278B2

Reaction notes

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