Cesium carbonate → HCID 25096955, compound

HRID 2080988Notes

Reaction equation

HRID 2080988 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F: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[CH:22]=[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]>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][NH:10][C:11]([CH:13]1[CH2:17][N:16]([C:21]2[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=2)[C:15](=[O:18])[N:14]1[CH3:19])=[O:12]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 122863-BromopyridineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 25096716HCID 25096716, compound

Product 1

HCID 25096955HCID 25096955, compoundYield 50%

Reagents, catalysts & solvents 3

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

Procedure

A solution of N-[(2-chloro-4-fluorophenyl)methyl]-3-methyl-2-oxo-4-imidazolidinecarboxamide (28.6 mg, 0.1 mmol) (prepared as described in Example 29) and 3-bromopyridine (15.8 mg, 0.1 mmol) in 1,4-dioxane (3 ml) was treated with cesium carbonate (81 mg, 0.25 mmol), Xantphos™ (4.3 mg, 0.075 mmol) and tris(dibenzylideneacetone)dipalladium(0) (2.3 mg, 0.025 mmol) and the mixture was heated under reflux under argon for 18 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 collected and dried to give N-[(2-chloro-4-fluorophenyl)methyl]-3-methyl-2-oxo-1-(3-pyridinyl)-4-imidazolidinecarboxamide (18 mg, 50%). LC/MS [M+H]+=363, retention time 1.68 minutes.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux under argon for 18 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 collected
  10. customdried

Sources & evidence

ORD record
ord-f3c8b75bc96842a589dc49d05026ca60
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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