Cesium carbonate → HCID 131728809, compound

HRID 2080990Notes

Reaction equation

HRID 2080990 reaction equation
CN1C(C(OC(C)(C)C)=O)CNC1=O.BrC1N=CC=CN=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.[CH3:70][N:71]1[CH:75]([C:76]([O:78]C(C)(C)C)=[O:77])[CH2:74][N:73]([C:83]2[N:88]=[CH:87][CH:86]=[CH:85][N:84]=2)[C:72]1=[O:89].[C:90]([OH:96])([C:92]([F:95])([F:94])[F:93])=[O:91].C(Cl)Cl>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]>[OH:96][C:90]([C:92]([F:95])([F:94])[F:93])=[O:91].[CH3:70][N:71]1[C@H:75]([C:76]([OH:78])=[O:77])[CH2:74][N:73]([C:83]2[N:84]=[CH:85][CH:86]=[CH:87][N:88]=2)[C:72]1=[O:89]

Participants

10

Reactant 6

HCID 10796Cesium carbonateHCID 783452-BromopyrimidineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 21863450Trifluoroacetic acid methylene chlorideHCID 67103398HCID 67103398, compoundHCID 671035641,1-Dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate

Product 1

HCID 131728809HCID 131728809, compound

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 (801 mg, 4 mmol) (prepared as described in step (iii) of Example 13, starting from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid) and 2-bromopyrimidine (636 mg, 4 mmol) in 1,4-dioxane (20 ml) was treated with cesium carbonate (1955 mg, 6 mmol), Xantphos™ (174 mg, 0.3 mmol) and tris(dibenzylideneacetone)dipalladium(0) (92 mg, 0.1 mmol) and the mixture was heated under reflux under argon for 1 hour. 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 0-20% methanol in ethyl acetate to 1,1-dimethylethyl 3-methyl-2-oxo-1-(2-pyrimidinyl)-4-imidazolidinecarboxylate (360 mg, 32%). LC/MS [M+H]+=279. (ii) A solution of 1,1-dimethylethyl 3-methyl-2-oxo-1-(2-pyrimidinyl)-4-imidazolidinecarboxylate (0.557 g, 2 mmol) in TFA/DCM (1:2, 7.5 ml) was stirred at room temperature for 6 hours. The solution was evaporated and the residue was dried to give crude (4S)-3-methyl-2-oxo-1-(2-pyrimidinyl)-4-imidazolidinecarboxylic acid TFA salt (assume ˜2 mmol) which was used in the next step. LC/MS [M+H]+=223.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux under argon for 1 hour
  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 0-20% methanol in ethyl acetate to 1,1-dimethylethyl 3-methyl-2-oxo-1-(2-pyrimidinyl)-4-imidazolidinecarboxylate (360 mg, 32%)
  8. customThe solution was evaporated
  9. customthe residue was dried

Sources & evidence

ORD record
ord-ef12befb3d6d453c86d857398600c206
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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