Cesium carbonate → 1-(2-cyano-3-pyridinyl)-N-[(2,4-dichlorophenyl)methyl]-3-methyl-2-oxo-4-imidazolidinecarboxamide

HRID 2081057Notes

Reaction equation

HRID 2081057 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][NH:10][C:11]([CH:13]1[CH2:17][NH:16][C:15](=[O:18])[N:14]1[CH3:19])=[O:12].Br[C:21]1[C:22]([C:27]#[N:28])=[N:23][CH:24]=[CH:25][CH:26]=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]>[C:27]([C:22]1[C:21]([N:16]2[CH2:17][CH:13]([C:11]([NH:10][CH2:9][C:3]3[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=3[Cl:1])=[O:12])[N:14]([CH3:19])[C:15]2=[O:18])=[CH:26][CH:25]=[CH:24][N:23]=1)#[N:28]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 8176943-Bromopyridine-2-carbonitrileHCID 25098283N-[(2,4-dichlorophenyl)methyl]-3-methyl-2-oxo-4-imidazolidinecarboxamide

Product 1

HCID 250962121-(2-cyano-3-pyridinyl)-N-[(2,4-dichlorophenyl)methyl]-3-methyl-2-oxo-4-imidazolidinecarboxamideYield 79.2%

Reagents, catalysts & solvents 3

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

Procedure

A suspension of N-[(2,4-dichlorophenyl)methyl]-3-methyl-2-oxo-4-imidazolidinecarboxamide (200 mg, 0.662 mmol) (prepared as described in Example 30) and 3-bromo-2-pyridinecarbonitrile (121 mg, 0.662 mmol) in 1,4-dioxane (5 ml) was treated with cesium carbonate (323 mg, 0.993 mmol), Xantphos™ (28.7 mg, 0.050 mmol) and tris(dibenzylideneacetone)dipalladium(0) (15.15 mg, 0.017 mmol) and the mixture was heated at reflux under argon for overnight. 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 10-100% ethyl acetate in isohexane to give 1-(2-cyano-3-pyridinyl)-N-[(2,4-dichlorophenyl)methyl]-3-methyl-2-oxo-4-imidazolidinecarboxamide (212 mg, 78% yield). LC/MS [M+H]+=404, retention time=2.32 minutes.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux under argon for overnight
  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 10-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-13e3b5b92d4842fd9447c3bf1ab1e17d
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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