Potassium Phosphate, Tribasic → N-[(2-chloro-3,4-difluorophenyl)methyl]-3-methyl-1-(1-methyl-1H-imidazol-2-yl)-2-oxo-4-imidazolidinecarboxamide

HRID 2080995Notes

Reaction equation

HRID 2080995 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[C:6]([F:9])[CH:5]=[CH:4][C:3]=1[CH2:10][NH:11][C:12]([CH:14]1[CH2:18][NH:17][C:16](=[O:19])[N:15]1[CH3:20])=[O:13].Br[C:22]1[N:23]([CH3:27])[CH:24]=[CH:25][N:26]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN(C)[C@@H]1CCCC[C@H]1N>O1CCOCC1.[Cu]I>[Cl:1][C:2]1[C:7]([F:8])=[C:6]([F:9])[CH:5]=[CH:4][C:3]=1[CH2:10][NH:11][C:12]([CH:14]1[CH2:18][N:17]([C:22]2[N:23]([CH3:27])[CH:24]=[CH:25][N:26]=2)[C:16](=[O:19])[N:15]1[CH3:20])=[O:13]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27732622-Bromo-1-methyl-1H-imidazoleHCID 11275066(1R,2R)-N1,N1-Dimethylcyclohexane-1,2-diamineHCID 25098282N-[(2-Chloro-3,4-difluorophenyl)methyl]-3-methyl-2-oxo-4-imidazolidinecarboxamide

Product 1

HCID 25096958N-[(2-chloro-3,4-difluorophenyl)methyl]-3-methyl-1-(1-methyl-1H-imidazol-2-yl)-2-oxo-4-imidazolidinecarboxamideYield 19.1%

Reagents, catalysts & solvents 2

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

Procedure

To a stirred mixture of N-[(2-chloro-3,4-difluorophenyl)methyl]-3-methyl-2-oxo-4-imidazolidinecarboxamide (91 mg, 0.3 mmol) (prepared as described in Example 28) and 2-bromo-1-methyl-1H-imidazole (48.3 mg, 0.3 mmol) in 1,4-dioxane (6 ml) was added potassium phosphate (318 mg, 1.5 mmol), copper (I) iodide (57.1 mg, 0.3 mmol) and trans-N,N-dimethylcyclohexane-1,2-diamine (0.047 ml, 0.3 mmol) and the mixture was heated at reflux under argon for 3 hours. The mixture was cooled to room temperature and partitioned between saturated sodium hydrogen carbonate solution and dichloromethane. The organic extracts were separated, washed with water and brine, dried and evaporated. The residue was purified by mass-directed automated HPLC to give N-[(2-chloro-3,4-difluorophenyl)methyl]-3-methyl-1-(1-methyl-1H-imidazol-2-yl)-2-oxo-4-imidazolidinecarboxamide (22 mg, 19%). LC/MS [M+H]+=384, retention time=1.69 minutes.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux under argon for 3 hours
  3. custompartitioned between saturated sodium hydrogen carbonate solution and dichloromethane
  4. customThe organic extracts were separated
  5. washwashed with water and brine
  6. customdried
  7. customevaporated
  8. customThe residue was purified

Sources & evidence

ORD record
ord-39f24a800bfa4dbba0fb6d57c1739357
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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