HCID 67103625, compound → HCID 67103624, compound

HRID 2081001Notes

Reaction equation

HRID 2081001 reaction equation
[CH3:1][N:2]1[CH:6]([C:7]([O:9]C(C)(C)C)=[O:8])[CH2:5][N:4]([C:14]2[CH:15]=[N:16][CH:17]=[N:18][CH:19]=2)[C:3]1=[O:20]>C(O)(C(F)(F)F)=O.C(Cl)Cl>[CH3:1][N:2]1[CH:6]([C:7]([OH:9])=[O:8])[CH2:5][N:4]([C:14]2[CH:19]=[N:18][CH:17]=[N:16][CH:15]=2)[C:3]1=[O:20]

Participants

3

Reactant 1

HCID 67103625HCID 67103625, compound

Product 1

HCID 67103624HCID 67103624, compoundYield 97.2%

Reagents, catalysts & solvents 1

HCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

A solution of 1,1-dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate (601 mg, 3 mmol) (prepared as described in step (iii) of Example 13, starting from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid) and 5-bromopyrimidine (477 mg, 3.00 mmol) in 1,4-dioxane (20 ml) was treated with cesium carbonate (1466 mg, 4.50 mmol), Xantphos™ (130 mg, 0.225 mmol) and tris(dibenzylideneacetone)dipalladium(0) (68.7 mg, 0.075 mmol) and the mixture was heated under reflux under argon for 3 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-2-oxo-1-(5-pyrimidinyl)-4-imidazolidinecarboxylate (349 mg, 42%). LC/MS [M+H]+=279. (ii) A solution of 1,1-dimethylethyl 3-methyl-2-oxo-1-(5-pyrimidinyl)-4-imidazolidinecarboxylate (630 mg, 2.264 mmol) in TFA/DCM (1:2, 9 ml) was stirred at room temperature for 8 hours. The solution was evaporated and the residue was co-evaporated with toluene and dried to give crude 3-methyl-2-oxo-1-(5-pyrimidinyl)-4-imidazolidinecarboxylic acid (assume ˜2.2 mmol) which was used in the next step. LC/MS [M+H]+=223.

Workup

  1. customThe solution was evaporated
  2. customdried

Sources & evidence

ORD record
ord-d6bed50114e9421d8a68a88276f0b8dc
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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