Trifluoroacetic acid → 3-Methyl-1-[4-(methyloxy)-2-pyrimidinyl]-2-oxo-4-imidazolidinecarboxylic acid

HRID 2081050Notes

Reaction equation

HRID 2081050 reaction equation
FC1C=NC(N2CC(C(OC(C)(C)C)=O)N(C)C2=O)=NC=1.[CH3:22][N:23]1[CH:27]([C:28]([O:30]C(C)(C)C)=[O:29])[CH2:26][N:25]([C:35]2[N:40]=[C:39]([O:41][CH3:42])[CH:38]=[CH:37][N:36]=2)[C:24]1=[O:43].FC(F)(F)C(O)=O>ClCCl>[CH3:22][N:23]1[CH:27]([C:28]([OH:30])=[O:29])[CH2:26][N:25]([C:35]2[N:40]=[C:39]([O:41][CH3:42])[CH:38]=[CH:37][N:36]=2)[C:24]1=[O:43]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 671031911,1-Dimethylethyl 1-(5-fluoro-2-pyrimidinyl)-3-methyl-2-oxo-4-imidazolidinecarboxylateHCID 671032461,1-Dimethylethyl 3-methyl-1-[4-(methyloxy)-2-pyrimidinyl]-2-oxo-4-imidazolidinecarboxylate

Product 1

HCID 671036213-Methyl-1-[4-(methyloxy)-2-pyrimidinyl]-2-oxo-4-imidazolidinecarboxylic acidYield 92.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1,1-dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate (500 mg, 2.497 mmol) (prepared as described in step (iii) of Example 13, starting from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid) and 2-chloro-4-(methyloxy)pyrimidine (361 mg, 2.497 mmol) in 1,4-dioxane (20 ml) was treated with cesium carbonate (1220 mg, 3.75 mmol), Xantphos™ (108 mg, 0.187 mmol) and tris(dibenzylideneacetone)dipalladium(0) (57.2 mg, 0.062 mmol) and the mixture was heated at reflux under argon for 3 hours. After cooling to room temperature, the reaction mixture was diluted with water (15 ml) and extracted with ethyl acetate (×2, 20 ml). The organic layers were combined, washed with water (20 ml) and brine (20 ml), dried over magnesium sulphate and then evaporated in vacuo. The residue was purified by flash-silica gel chromatography eluting with 0-10% methanol in dichloromethane. The fractions containing product were combined and solvent evaporated in vacuo to give a yellow oil. The residue was purified again by flash-silica gel chromatography, eluting with 0-100% ethyl acetate in isohexane to give 1,1-dimethylethyl 3-methyl-1-[4-(methyloxy)-2-pyrimidinyl]-2-oxo-4-imidazolidinecarboxylate as a yellow oil (100 mg, 13% yield). LC/MS [M+H]+309. (ii) A solution of 1,1-dimethylethyl 3-methyl-1-[4-(methyloxy)-2-pyrimidinyl]-2-oxo-4-imidazolidinecarboxylate (100 mg, 0.324 mmol) in dichloromethane (0.6 ml)/trifluoroacetic acid (0.300 ml) was stirred at room temperature for 24 hours. The solution was evaporated and the residue was co-evaporated with toluene (×3) and then dichloromethane (×4). The product was then dried in a vacuum oven (50° C.) to give crude 3-methyl-1-[4-(methyloxy)-2-pyrimidinyl]-2-oxo-4-imidazolidinecarboxylic acid as a yellow gum (95 mg, ˜0.3 mmol) which was used in the next reaction. LC/MS [M+H]+253.

Workup

  1. customThe solution was evaporated
  2. customThe product was then dried in a vacuum oven (50° C.)

Sources & evidence

ORD record
ord-5d2ceb1586114310aec75ea4666752b8
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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