Cesium carbonate → HCID 67103419, compound

HRID 2080975Notes

Reaction equation

HRID 2080975 reaction equation
[CH3:1][N:2]1[CH:6]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:5][NH:4][C:3]1=[O:14].Br[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH3:22])[N:17]=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.O.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]>[CH3:1][N:2]1[CH:6]([C:7]([O:9][C:10]([CH3:11])([CH3:13])[CH3:12])=[O:8])[CH2:5][N:4]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([CH3:22])[N:17]=2)[C:3]1=[O:14]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 792052-Bromo-6-methylpyridineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 671035641,1-Dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate

Product 1

HCID 67103419HCID 67103419, compoundYield 56.3%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 1,1-dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate (300 mg, 1.5 mmol) (prepared as described in step (iii) of Example 13, starting from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid) and 2-bromo-6-methylpyridine (258 mg, 1.5 mmol) in 1,4-dioxane (10 ml) was treated with cesium carbonate (733 mg, 2.25 mmol), Xantphos™ (65.1 mg, 0.113 mmol) and tris(dibenzylideneacetone)dipalladium(0) (34.3 mg, 0.038 mmol) and the mixture was heated under reflux under argon for 18 hours. After cooling to room temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layers were combined, washed with water and brine and evaporated in vacuo. The residue was purified by silica gel chromatography eluting with 0-100% ethyl acetate in isohexane to give 1,1-dimethylethyl 3-methyl-1-(6-methyl-2-pyridinyl)-2-oxo-4-imidazolidinecarboxylate (246 mg, 56%). LC/MS [M+H]+=292. (ii) A solution of 1,1-dimethylethyl 3-methyl-1-(6-methyl-2-pyridinyl)-2-oxo-4-imidazolidinecarboxylate (246 mg, 0.84 mmol) in TFA/DCM (1:2, 6 ml) was stirred at room temperature for 6 hours. The solution was evaporated and the residue was dried to give 3-methyl-1-(6-methyl-2-pyridinyl)-2-oxo-4-imidazolidinecarboxylic acid TFA salt (assume ˜0.84 mmol) which was used in the next step. LC/MS [M+H]+=236.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux under argon for 18 hours
  3. extractionextracted with ethyl acetate
  4. washwashed with water and brine
  5. customevaporated in vacuo
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with 0-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-04a989cc2b444c1fbe675a4c439cf480
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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