Cesium carbonate → HCID 25096956, compound

HRID 2080991Notes

Reaction equation

HRID 2080991 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[CH:27]=[CH:26][N:25]=[C:24]([CH3:28])[CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C(=O)([O-])O.[Na+].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[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[CH:27]=[CH:26][N:25]=[C:24]([CH3:28])[CH:23]=2)[C:16](=[O:19])[N:15]1[CH3:20])=[O:13]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27628354-Bromo-2-methylpyridineHCID 25098282N-[(2-Chloro-3,4-difluorophenyl)methyl]-3-methyl-2-oxo-4-imidazolidinecarboxamide

Product 1

HCID 25096956HCID 25096956, compoundYield 62.3%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A solution of N-[(2-chloro-3,4-difluorophenyl)methyl]-3-methyl-2-oxo-4-imidazolidinecarboxamide (152 mg, 0.5 mmol) (prepared as described in Example 28) and 4-bromo-2-methylpyridine (86 mg, 0.5 mmol) in 1,4-dioxane (3 ml) was treated with cesium carbonate (244 mg, 0.75 mmol), Xantphos™ (21.7 mg, 0.038 mmol) and tris(dibenzylideneacetone)dipalladium(0) (11.5 mg, 0.013 mmol) and the mixture was heated under reflux under argon for 3 hours. After cooling to room temperature, the reaction mixture was diluted with saturated sodium hydrogen carbonate solution and extracted with dichloromethane. The organic layers were combined, washed with water and brine and evaporated in vacuo. The residue was purified by silica gel chromatography eluting with 0-10% methanol in dichloromethane. The resulting residue was triturated with ether, the solid was collected and dried to give N-[(2-chloro-3,4-difluorophenyl)methyl]-3-methyl-1-(2-methyl-4-pyridinyl)-2-oxo-4-imidazolidinecarboxamide (123 mg, 62%). LC/MS [M+H]+=395, retention time=1.68 minutes.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux under argon for 3 hours
  3. extractionextracted with dichloromethane
  4. washwashed with water and brine
  5. customevaporated in vacuo
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with 0-10% methanol in dichloromethane
  8. customThe resulting residue was triturated with ether
  9. customthe solid was collected
  10. customdried

Sources & evidence

ORD record
ord-cded186b0fa344fd9ac2842f54ca86c9
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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