Water → 4-[3-[3,6-Dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl]thiophen-2-yl]benzonitrile

HRID 576759Notes

Reaction equation

HRID 576759 reaction equation
Br[C:2]1[S:3][CH:4]=[CH:5][C:6]=1[C:7]1[C:8](=[O:26])[N:9]([CH3:25])[C:10](=[O:24])[N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=2)[C:12]=1[CH3:13].[C:27]([C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1)#[N:28].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>[CH3:25][N:9]1[C:8](=[O:26])[C:7]([C:6]2[CH:5]=[CH:4][S:3][C:2]=2[C:32]2[CH:33]=[CH:34][C:29]([C:27]#[N:28])=[CH:30][CH:31]=2)=[C:12]([CH3:13])[N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=2)[C:10]1=[O:24]

Participants

7

Reactant 4

HCID 962Water2×HCID 10340Sodium CarbonateHCID 27343264-Cyanophenylboronic acidHCID 867238575-(2-bromothiophen-3-yl)-3,6-dimethyl-1-(3-trifluoromethylphenyl)pyrimidin-2,4(1H,3H)-dione

Product 1

HCID 867238584-[3-[3,6-Dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl]thiophen-2-yl]benzonitrileYield 91.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-(2-bromothiophen-3-yl)-3,6-dimethyl-1-(3-trifluoromethylphenyl)pyrimidin-2,4(1H,3H)-dione (prepared in Reference Example 200) (17.0 mg), 4-cyanophenylboronic acid (11.2 mg) and sodium carbonate (20.2 mg) in tetrahydrofuran (1.0 ml)/water (0.2 ml) was added tetrakis(triphenylphosphine)palladium (4.4 mg) and the resulting mixture was stirred with heating under reflux for twelve 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 (10 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-[3-[3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl]thiophen-2-yl]benzonitrile (16.4 mg).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for twelve hours
  3. extractionthe resulting mixture was extracted with ethyl acetate (10 ml×2)
  4. washThe organic layer was washed with saturated saline (10 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-7a4b567622904193afd40cc236f74400
Source dataset
uspto-grants-2015_05
Patent number
US09040516B2

Reaction notes

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