Potassium Phosphate, Tribasic → N-[(2-chloro-3,4-difluorophenyl)methyl]-3-methyl-1-(1-methyl-1H-pyrazol-5-yl)-2-oxo-4-imidazolidinecarboxamide

HRID 2080996Notes

Reaction equation

HRID 2080996 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].I[C:22]1[N:26]([CH3:27])[N:25]=[CH:24][CH:23]=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:26]([CH3:27])[N:25]=[CH:24][CH:23]=2)[C:16](=[O:19])[N:15]1[CH3:20])=[O:13]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 11275066(1R,2R)-N1,N1-Dimethylcyclohexane-1,2-diamineHCID 133340655-Iodo-1-methyl-1H-pyrazoleHCID 25098282N-[(2-Chloro-3,4-difluorophenyl)methyl]-3-methyl-2-oxo-4-imidazolidinecarboxamide

Product 1

HCID 25094347N-[(2-chloro-3,4-difluorophenyl)methyl]-3-methyl-1-(1-methyl-1H-pyrazol-5-yl)-2-oxo-4-imidazolidinecarboxamideYield 23.5%

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 (60.7 mg, 0.2 mmol) (prepared as described in Example 28), 5-iodo-1-methyl-1H-pyrazole (41.6 mg, 0.2 mmol) in 1,4-dioxane (4 ml) was added potassium phosphate (212 mg, 1 mmol), copper (I) iodide (38.1 mg, 0.2 mmol) and trans-N,N-dimethylcyclohexane-1,2-diamine (0.032 ml, 0.2 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 mass-directed automated HPLC to give N-[(2-chloro-3,4-difluorophenyl)methyl]-3-methyl-1-(1-methyl-1H-pyrazol-5-yl)-2-oxo-4-imidazolidinecarboxamide (18 mg, 23%). LC/MS [M+H]+=384, retention time=2.22 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

Sources & evidence

ORD record
ord-1f00cd7402774adb9e5c2b78fffa338e
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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