Potassium Phosphate, Tribasic → HCID 67103428, compound

HRID 2081027Notes

Reaction equation

HRID 2081027 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].[F:15][C:16]1[C:21](I)=[CH:20][CH:19]=[CH:18][N:17]=1.CN(C)[C@@H]1CCCC[C@H]1N.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.[Cu]I>[F:15][C:16]1[C:21]([N:4]2[CH2:5][CH:6]([C:7]([O:9][C:10]([CH3:11])([CH3:13])[CH3:12])=[O:8])[N:2]([CH3:1])[C:3]2=[O:14])=[CH:20][CH:19]=[CH:18][N:17]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 70095012-Fluoro-3-iodopyridineHCID 11275066(1R,2R)-N1,N1-Dimethylcyclohexane-1,2-diamineHCID 671035641,1-Dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate

Product 1

HCID 67103428HCID 67103428, compoundYield 68.6%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 1,1-dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate (400 mg, 1.998 mmol) (prepared as described in step (iii) of Example 13, starting from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid) and 2-fluoro-3-iodopyridine (352 mg, 1.998 mmol) in 1,4-dioxane (20 ml) was added trans-N,N-dimethylcyclohexane-1,2-diamine (0.062 ml, 0.400 mmol), potassium phosphate (1272 mg, 5.99 mmol) and copper(I) iodide (38.0 mg, 0.200 mmol) and the reaction mixture was heated at reflux under argon overnight. The reaction mixture was allowed to cool and the solvent was evaporated. The residue was partitioned between dichloromethane and water. The organic layer was separated and washed with water (˜50 ml) containing 0.880 ammonia solution (˜5 ml), then brine and passed through a hydrophobic frit and the organic layer was reduced under vacuum. The residue was purified by SP4 automated silica gel chromatography eluting with 10-80% ethyl acetate in isohexane to give 1,1-dimethylethyl 1-(2-fluoro-3-pyridinyl)-3-methyl-2-oxo-4-imidazolidinecarboxylate (405 mg, 67.3% yield). LC/MS [M+H]+=296. (ii) Trifluoroacetic acid (2 ml) was added to a solution of 1,1-dimethylethyl (4S)-1-(2-fluoro-3-pyridinyl)-3-methyl-2-oxo-4-imidazolidinecarboxylate (400 mg, 1.355 mmol) in dichloromethane (5 ml) and the solution was stirred at room temperature for 36 hours. The reaction mixture was reduced under vacuum and the residue was azeotroped with toluene and dried under heated vacuum to give 1-(2-fluoro-3-pyridinyl)-3-methyl-2-oxo-4-imidazolidinecarboxylic acid TFA salt (assume ˜1.35 mmol) which was used in the next step. LC/MS [M+H]+=240.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux under argon overnight
  3. temperatureto cool
  4. customthe solvent was evaporated
  5. customThe residue was partitioned between dichloromethane and water
  6. customThe organic layer was separated
  7. washwashed with water (˜50 ml)
  8. additioncontaining 0.880 ammonia solution (˜5 ml)
  9. customThe residue was purified by SP4 automated silica gel chromatography
  10. washeluting with 10-80% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-a1b019fc674b4720a4eae0fa321d4637
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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