Water → 3,6-dimethyl-5-(thiophen-3-yl)-1-(3-trifluoromethylphenyl)pyrimidin-2,4(1H,3H)-dione

HRID 576757Notes

Reaction equation

HRID 576757 reaction equation
I[C:2]1[C:3](=[O:21])[N:4]([CH3:20])[C:5](=[O:19])[N:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[C:7]=1[CH3:8].[S:22]1[CH:26]=[CH:25][CH:24]=[C:23]1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].O>O1CCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:20][N:4]1[C:3](=[O:21])[C:2]([C:24]2[CH:25]=[CH:26][S:22][CH:23]=2)=[C:7]([CH3:8])[N:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[C:5]1=[O:19]

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27339602-Thiopheneboronic acidHCID 867238385-iodo-3,6-dimethyl-1-(3-trifluoromethylphenyl)pyrimidin-2,4(1H,3H)-dione

Product 1

HCID 867238563,6-dimethyl-5-(thiophen-3-yl)-1-(3-trifluoromethylphenyl)pyrimidin-2,4(1H,3H)-dioneYield 50.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-iodo-3,6-dimethyl-1-(3-trifluoromethylphenyl)pyrimidin-2,4(1H,3H)-dione (prepared in Reference Example 60) (60.0 mg), 2-thiophen boronic acid (84.6 mg), sodium carbonate (84.6 mg) in tetrahydrofuran (2.0 ml)/water (0.3 ml) was added tetrakis(triphenylphosphine)palladium (25.2 mg) and the resulting mixture was stirred with heating under reflux for five hours. The reaction mixture was filtered through Celite (trade mark) and thereto 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: chloroform/methanol) to afford 3,6-dimethyl-5-(thiophen-3-yl)-1-(3-trifluoromethylphenyl)pyrimidin-2,4(1H,3H)-dione (27.3 mg).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for five hours
  3. filtrationThe reaction mixture was filtered through Celite (trade mark)
  4. additionwas added water (10 ml)
  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: chloroform/methanol)

Sources & evidence

ORD record
ord-c079ccc604564adb82aaa61e1de8cc68
Source dataset
uspto-grants-2015_05
Patent number
US09040516B2

Reaction notes

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