2-Bromopyridine → HCID 67103421, compound

HRID 2080981Notes

Reaction equation

HRID 2080981 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]=[CH:18][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]=[CH:18][N:17]=2)[C:3]1=[O:14]

Participants

8

Reactant 4

HCID 79732-BromopyridineHCID 10796Cesium carbonateHCID 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 67103421HCID 67103421, compoundYield 36%

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 (400 mg, 2 mmol) (prepared as described in step (iii) of Example 13) and 2-bromopyridine (316 mg, 2 mmol) in 1,4-dioxane (10 ml) was treated with cesium carbonate (977 mg, 3 mmol), Xantphos™ (87 mg, 0.15 mmol) and tris(dibenzylideneacetone)dipalladium(0) (45.8 mg, 0.05 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 (2 columns required) to give 1,1-dimethylethyl 3-methyl-2-oxo-1-(2-pyridinyl)-4-imidazolidinecarboxylate (198 mg, 36%). LC/MS [M+H]+=278. (ii) A solution of 1,1-dimethylethyl 3-methyl-2-oxo-1-(2-pyridinyl)-4-imidazolidinecarboxylate (198 mg, 0.71 mmol) in TFA/DCM (1:2, 4.5 ml) was stirred at room temperature for 8 hours. The solution was evaporated and the residue was dried to give 3-methyl-2-oxo-1-(2-pyridinyl)-4-imidazolidinecarboxylic acid TFA salt (assume ˜0.71 mmol)) which was used in the next step. LC/MS [M+H]+=222.

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 (2 columns required)

Sources & evidence

ORD record
ord-77d019eeb1604dcf8fdfc20ab9849c74
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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