Potassium Phosphate, Tribasic → HCID 67103394, compound

HRID 2081018Notes

Reaction equation

HRID 2081018 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:20]([CH3:21])[CH:19]=[N:18][CH:17]=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:20]([CH3:21])[CH:19]=[N:18][CH:17]=2)[C:3]1=[O:14]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 15152585-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 67103394HCID 67103394, compoundYield 35%

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 (801 mg, 4.00 mmol) (prepared as described in step (iii) of Example 13, starting from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid) and 5-bromo-1-methylimidazole (644 mg, 4.00 mmol) in 1,4-dioxane (30 ml) was added potassium phosphate (4246 mg, 20.00 mmol), trans-N,N-dimethylcyclohexane-1,2-diamine (0.631 ml, 4.00 mmol) and copper(I) iodide (762 mg, 4.00 mmol) and the mixture stirred at reflux overnight. The reaction mixture was diluted with dichloromethane and filtered through celite. The filter pad was washed with dichloromethane and the filtrate was reduced under vacuum. The residue was re-dissolved in dichloromethane, washed with 0.880 ammonia (×2), water then brine and passed through a hydrophobic frit and the solution was concentrated 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-5-yl)-2-oxo-4-imidazolidinecarboxylate (393 mg, 32.6% yield). LC/MS [M+H]+=281. (ii) Trifluoroacetic acid (2 ml) was added to a solution of 1,1-dimethylethyl (4S)-3-methyl-1-(1-methyl-1H-imidazol-5-yl)-2-oxo-4-imidazolidinecarboxylate (390 mg, 1.391 mmol) in dichloromethane (4 ml) and stirred at room temperature for 2 hours, then allowed to stand overnight. The solvent was evaporated and the residue was co-evaporated with toluene and dried under heated vacuum (40° C.) overnight to give 3-methyl-1-(1-methyl-1H-imidazol-5-yl)-2-oxo-4-imidazolidinecarboxylic acid TFA salt (assume ˜1.4 mmol) which was used which was used in the next step. LC/MS [M+H]+=225.

Workup

  1. temperatureat reflux overnight
  2. filtrationfiltered through celite
  3. washThe filter pad was washed with dichloromethane
  4. dissolutionThe residue was re-dissolved in dichloromethane
  5. washwashed with 0.880 ammonia (×2), water
  6. concentrationthe solution was concentrated under vacuum
  7. customThe residue was purified by Flashmaster automated silica gel chromatography
  8. washeluting with 0-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-967b3b86f8ac45c7b0eb59aa74f63c10
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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