Sodium Thiosulfate → 4-(4-chloro-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrile

HRID 576811Notes

Reaction equation

HRID 576811 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[C:6]([C:9]2[N:13]([C:14]3[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=3)[N:12]=[CH:11][CH:10]=2)=[C:5]([CH3:22])[N:4]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=2)[C:3]1=[O:33].[Cl-:34].[Li+].[N+]([O-])(O)=O.[N+]([O-])(O)=O.[N+]([O-])(O)=O.[N+]([O-])(O)=O.[N+]([O-])(O)=O.[N+]([O-])(O)=O.[Ce].S([O-])([O-])(=O)=S.[Na+].[Na+]>C(#N)C.C(OCC)(=O)C.C(O)(=O)C>[Cl:34][C:10]1[CH:11]=[N:12][N:13]([C:14]2[CH:15]=[CH:16][C:17]([C:18]#[N:19])=[CH:20][CH:21]=2)[C:9]=1[C:6]1[C:7](=[O:8])[N:2]([CH3:1])[C:3](=[O:33])[N:4]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:30])([F:31])[F:32])[CH:24]=2)[C:5]=1[CH3:22]

Participants

8

Reactant 4

HCID 24477Sodium ThiosulfateHCID 407333Cerate(2-), hexakis(nitrato-kappaO)-, potassium (1:2), (OC-6-11)-HCID 433294Lithium ChlorideHCID 712514174-[5-[3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl]-1H-pyrazol-1-yl]benzonitrile

Product 1

HCID 715143314-(4-chloro-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrileYield 107.9%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrile (prepared in Example 1) (205 mg) in acetonitrile (10 ml) were added lithium chloride (23 mg), ammonium hexanitrato cerate(IV) (498 mg) and acetic acid (2.5 ml) and the resulting mixture was stirred with heating under reflux for five hours. To the reaction mixture was 10% aqueous sodium thiosulfate solution (10 ml) followed by an addition of ethyl acetate (20 ml×2) such that the intended products were extracted into an organic layer. The organic layer was washed with saturated saline (20 ml), dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate) to afford 4-(4-chloro-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrile (238 mg). UPLC/MS 486 (M+H)/1.13 min (measurement condition 9)

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for five hours
  3. extractionwere extracted into an organic layer
  4. washThe organic layer was washed with saturated saline (20 ml)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate)

Sources & evidence

ORD record
ord-24c0bdbb9a634b1d94161119c2f240c7
Source dataset
uspto-grants-2015_05
Patent number
US09040516B2

Reaction notes

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