Potassium Phosphate, Tribasic → 1,1-dimethylethyl 3-methyl-1-(1-methyl-1H-imidazol-2-yl)-2-oxo-4-imidazolidinecarboxylate

HRID 2081015Notes

Reaction equation

HRID 2081015 reaction equation
[CH3:1][N:2]1[CH:6]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:5][NH:4][C:3]1=[O:14].Br[C:16]1[N:17]([CH3:21])[CH:18]=[CH:19][N:20]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN(C)[C@@H]1CCCC[C@H]1N>O1CCOCC1.ClCCl.[Cu]I>[CH3:1][N:2]1[CH:6]([C:7]([O:9][C:10]([CH3:11])([CH3:13])[CH3:12])=[O:8])[CH2:5][N:4]([C:16]2[N:17]([CH3:21])[CH:18]=[CH:19][N:20]=2)[C:3]1=[O:14]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27732622-Bromo-1-methyl-1H-imidazoleHCID 11275066(1R,2R)-N1,N1-Dimethylcyclohexane-1,2-diamineHCID 671035641,1-Dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate

Product 1

HCID 671033971,1-dimethylethyl 3-methyl-1-(1-methyl-1H-imidazol-2-yl)-2-oxo-4-imidazolidinecarboxylateYield 51.7%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of 1,1-dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate (0.200 g, 1.00 mmol) (prepared as described in step (iii) of Example 13, starting from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid) and 2-bromo-1-methyl-1H-imidazole (0.146 ml, 1.500 mmol) in 1,4-dioxane (8 ml) was added potassium phosphate (1.062 g, 5.00 mmol), copper(I) iodide (0.190 g, 1.000 mmol) and trans-N,N-dimethylcyclohexane-1,2-diamine (0.155 ml, 1.000 mmol) and the mixture heated at reflux under argon overnight. The mixture was cooled to room temperature and diluted with dichloromethane. The solid was filtered off, washed with dichloromethane and the filtrate reduced under vacuum. The residue was re-dissolved in dichloromethane and washed with 0.880 ammonia solution (×2), water then brine and passed through a hydrophobic frit and the organic layer reduced under vacuum. The residue was purified by Flashmaster automated silica gel chromatography eluting with 0-10% methanol in dichloromethane to give 1,1-dimethylethyl 3-methyl-1-(1-methyl-1H-imidazol-2-yl)-2-oxo-4-imidazolidinecarboxylate (145 mg, 37.8% yield). LC/MS [M+H]+=281. (ii) Trifluoroacetic acid (0.059 ml, 0.517 mmol) was added to a solution of 1,1-dimethylethyl 3-methyl-1-(1-methyl-1H-imidazol-2-yl)-2-oxo-4-imidazolidinecarboxylate (145 mg, 0.517 mmol) in DCM (2 ml) and the reaction stirred at room temperature overnight. The reaction mixture was co-evaporated with toluene and dried to give 3-methyl-1-(1-methyl-1H-imidazol-2-yl)-2-oxo-4-imidazolidinecarboxylic acid (assume ˜0.517 mmol) which was used which was used in the next step. LC/MS [M+H]+=225.

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux under argon overnight
  3. filtrationThe solid was filtered off
  4. washwashed with dichloromethane
  5. dissolutionThe residue was re-dissolved in dichloromethane
  6. washwashed with 0.880 ammonia solution (×2), water
  7. customThe residue was purified by Flashmaster automated silica gel chromatography
  8. washeluting with 0-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-7927d25965e54083a4551406bff4bc8f
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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