Dimethylformamide → 4'-{[3-(2-cyclohexyl-2-oxoethyl)-2,4-dioxo-6-(2,2,2-trifluoroethyl)-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}biphenyl-2-carbonitrile

HRID 1889385Notes

Reaction equation

HRID 1889385 reaction equation
[O:1]=[C:2]1[N:7]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[C:16]([C:21]#[N:22])=[CH:17][CH:18]=[CH:19][CH:20]=3)=[CH:11][CH:10]=2)[C:6]2[S:23][C:24]([CH2:26][C:27]([F:30])([F:29])[F:28])=[CH:25][C:5]=2[C:4](=[O:31])[NH:3]1.[CH:32]1([CH:38]2[CH2:40][O:39]2)[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1.CN(C)C=O.C(=O)([O-])[O-].[K+].[K+]>O.C(OCC)(=O)C>[CH:32]1([C:38](=[O:39])[CH2:40][N:3]2[C:4](=[O:31])[C:5]3[CH:25]=[C:24]([CH2:26][C:27]([F:30])([F:29])[F:28])[S:23][C:6]=3[N:7]([CH2:8][C:9]3[CH:10]=[CH:11][C:12]([C:15]4[C:16]([C:21]#[N:22])=[CH:17][CH:18]=[CH:19][CH:20]=4)=[CH:13][CH:14]=3)[C:2]2=[O:1])[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 942642-CyclohexyloxiraneHCID 593517254'-{[2,4-dioxo-6-(2,2,2-trifluoroethyl)-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}biphenyl-2-carbonitrile

Product 1

HCID 593516784'-{[3-(2-cyclohexyl-2-oxoethyl)-2,4-dioxo-6-(2,2,2-trifluoroethyl)-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}biphenyl-2-carbonitrileYield 79%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 4′-{[2,4-dioxo-6-(2,2,2-trifluoroethyl)-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}biphenyl-2-carbonitrile (1.0 g), 2-cyclohexyloxirane (0.98 g) and N,N-dimethylformamide (7 mL) was added potassium carbonate (0.63 g), and the mixture was stirred at 80° C. for 24 hr. To the reaction mixture was added ethyl acetate and water, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. A mixture of the obtained residue, tetrapropylammonium perruthenate (0.011 g), 4-methylmorpholine-N-oxide (0.15 g), molecular sieves 4A (0.12 g) and methylene chloride (3 mL) was stirred at room temperature for 24 hr. The reaction mixture was purified by silica gel column chromatography to give the title compound as a pale-yellow amorphous solid (0.29 g, 79%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. additionA mixture of the obtained residue, tetrapropylammonium perruthenate (0.011 g), 4-methylmorpholine-N-oxide (0.15 g), molecular sieves 4A (0.12 g) and methylene chloride (3 mL)
  6. stirringwas stirred at room temperature for 24 hr
  7. customThe reaction mixture was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-5daf509f024c4e41ae2cf8ce661e644d
Source dataset
uspto-grants-2013_08
Patent number
US08501750B2

Reaction notes

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