Water → HCID 86723859, compound

HRID 576760Notes

Reaction equation

HRID 576760 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[C:6]([C:9]2[NH:10][CH:11]=[CH:12][CH:13]=2)=[C:5]([CH3:14])[N:4]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)[C:3]1=[O:25].[C:26]([C:28]1[CH:33]=[CH:32][C:31](I)=[CH:30][CH:29]=1)#[N:27].P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>O1CCOCC1.[Cu]I>[CH3:1][N:2]1[C:7](=[O:8])[C:6]([C:9]2[N:10]([C:31]3[CH:32]=[CH:33][C:28]([C:26]#[N:27])=[CH:29][CH:30]=3)[CH:11]=[CH:12][CH:13]=2)=[C:5]([CH3:14])[N:4]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:23])([F:24])[F:22])[CH:16]=2)[C:3]1=[O:25]

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, Tribasic2×HCID 764674-Iodobenzonitrile2×HCID 86723860HCID 86723860, compound

Product 1

HCID 86723859HCID 86723859, compoundYield 31.8%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 312751,4-DioxaneSolvent

Procedure

A solution of 3,6-dimethyl-5(1H-pyrrol-2-yl)-1-(3-trifluoromethylphenyl)pyrimidin-2,4(1H,3H)-dione (prepared in Reference Example 201) (20.0 mg), 4-cyanoiodobenzene (39.4 mg), copper(I) iodide (1.0 mg), cyclohexyldiamine (0.6 mg) and potassium phosphate (36.4 mg) in 1,4-dioxane (2.0 ml) was stirred with heating under reflux for fifteen hours. Thereto were added 4-cyanoiodobenzene (39.4 mg), copper(I) iodide (1.0 mg), cyclohexyldiamine (0.6 mg) and potassium phosphate (36.4 mg) and the resulting mixture was stirred with heating under reflux for four hours. To the reaction mixture was added water (10 ml) and the resulting mixture was extracted with ethyl acetate (10 ml×2). 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) and further purified by silica gel column chromatography (eluent: hexane/acetone/methanol) to afford 4-[2-[3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl]-1H-pyrrol-1-yl]benzonitrile (8.2 mg).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for fifteen hours
  3. temperaturewith heating
  4. temperatureunder reflux for four hours
  5. extractionthe resulting mixture was extracted with ethyl acetate (10 ml×2)
  6. washThe organic layer was washed with saturated saline (20 ml)
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate)
  10. customfurther purified by silica gel column chromatography (eluent: hexane/acetone/methanol)

Sources & evidence

ORD record
ord-2829a6ec04974b1d88c5e4ee2af6ad06
Source dataset
uspto-grants-2015_05
Patent number
US09040516B2

Reaction notes

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