Dichloromethane → HCID 67103401, compound

HRID 2081022Notes

Reaction equation

HRID 2081022 reaction equation
FC(F)(F)C(O)=O.[CH3:8][N:9]1[CH:13]([C:14]([O:16]C(C)(C)C)=[O:15])[CH2:12][N:11]([C:21]2[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[N:24]=[CH:23][N:22]=2)[C:10]1=[O:31].[Cl:32]CCl>>[ClH:32].[CH3:8][N:9]1[CH:13]([C:14]([OH:16])=[O:15])[CH2:12][N:11]([C:21]2[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[N:24]=[CH:23][N:22]=2)[C:10]1=[O:31]

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 67103623HCID 67103623, compound

Product 1

HCID 67103401HCID 67103401, compound

Procedure

A solution of 1,1-dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate (800 mg, 4.00 mmol) (prepared as described in step (iii) of Example 13, starting from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid) and 4-chloro-6-(trifluoromethyl)pyrimidine (729 mg, 4.00 mmol) in 1,4-dioxane (40 ml) was treated with cesium carbonate (1953 mg, 5.99 mmol), Xantphos™ (173 mg, 0.300 mmol) and tris(dibenzylideneacetone)dipalladium(0) (91 mg, 0.100 mmol) and the reaction mixture was heated at reflux under argon overnight. After cooling the reaction was diluted with water and extracted with ethyl acetate (×2). The organic layers were combined and washed with water and brine, dried over anhydrous sodium sulfate and reduced under vacuum. The residue was purified by Flashmaster automated silica gel chromatography eluting with 0-30% ethyl acetate in isohexane to give 1,1-dimethylethyl 3-methyl-2-oxo-1-[6-(trifluoromethyl)-4-pyrimidinyl]-4-imidazolidinecarboxylate (983 mg, 67.5% yield). LC/MS [M+H]+=347. (ii) Trifluoroacetic acid (4 ml, 51.9 mmol) was added to a solution of 1,1-dimethylethyl 3-methyl-2-oxo-1-[6-(trifluoromethyl)-4-pyrimidinyl]-4-imidazolidinecarboxylate (980 mg, 2.83 mmol) in dichloromethane (8 ml) and the solution was stirred at room temperature for 6 hours. The solvent was evaporated and the residue was co-evaporated with toluene. The residue was dissolved in saturated sodium hydrogen carbonate solution and the solution was loaded onto an amino column eluting with 10% 2N hydrochloric acid in methanol. Product-containing fractions were combined and reduced under vacuum and the residue was triturated with methanol and the solid was filtered off. The filtrate was reduced under vacuum to give 3-methyl-2-oxo-1-[6-(trifluoromethyl)-4-pyrimidinyl]-4-imidazolidinecarboxylic acid hydrochloride salt (893 mg, assume ˜2.8 mmol) which was used in the next step. LC/MS [M+H]+=291.

Workup

  1. customThe solvent was evaporated
  2. dissolutionThe residue was dissolved in saturated sodium hydrogen carbonate solution
  3. washeluting with 10% 2N hydrochloric acid in methanol
  4. customthe residue was triturated with methanol
  5. filtrationthe solid was filtered off

Sources & evidence

ORD record
ord-46bc63dc8ad340a28c5defa32d41ca1e
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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