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

HRID 2080994Notes

Reaction equation

HRID 2080994 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]=[CH:24][N:25]([CH3:27])[CH: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]=[CH:24][N:25]([CH3:27])[CH:26]=2)[C:16](=[O:19])[N:15]1[CH3:20])=[O:13]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 12776534-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 25094346N-[(2-chloro-3,4-difluorophenyl)methyl]-3-methyl-1-(1-methyl-1H-imidazol-4-yl)-2-oxo-4-imidazolidinecarboxamideYield 12%

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 (100 mg, 0.33 mmol) (prepared as described in Example 28), 4-bromo-1-methyl-1H-imidazole (63.8 mg, 0.396 mmol) in 1,4-dioxane (6 ml) was added potassium phosphate (350 mg, 1.65 mmol), copper (I) iodide (62.8 mg, 0.33 mmol) and trans-N,N-dimethylcyclohexane-1,2-diamine (0.052 ml, 0.33 mmol) and the mixture was heated at reflux under argon for 1 h. 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 silica gel chromatography eluting with 0-20% methanol in dichloromethane, followed by mass-directed automated HPLC to give N-[(2-chloro-3,4-difluorophenyl)methyl]-3-methyl-1-(1-methyl-1H-imidazol-4-yl)-2-oxo-4-imidazolidinecarboxamide (15 mg, 12%). LC/MS [M+H]+=384, retention time=1.71 minutes.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux under argon for 1 h
  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 by silica gel chromatography
  9. washeluting with 0-20% methanol in dichloromethane

Sources & evidence

ORD record
ord-146da24030874e289a642aa858454c7a
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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