Dimethyl Sulfoxide → 3-(2-cyclohexyl-2-oxoethyl)-1-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 1889522Notes

Reaction equation

HRID 1889522 reaction equation
[Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[CH:13]1([C:19](=[O:52])[CH2:20][N:21]2[C:26](=[O:27])[C:25]3[CH:28]=[C:29]([CH2:31][C:32]([F:35])([F:34])[F:33])[S:30][C:24]=3[N:23]([CH2:36][C:37]3[CH:42]=[CH:41][C:40]([C:43]4[C:44]([C:49]#[N:50])=[CH:45][CH:46]=[CH:47][CH:48]=4)=[CH:39][CH:38]=3)[C:22]2=[O:51])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1>O.C(OCC)(=O)C>[CH:13]1([C:19](=[O:52])[CH2:20][N:21]2[C:26](=[O:27])[C:25]3[CH:28]=[C:29]([CH2:31][C:32]([F:34])([F:35])[F:33])[S:30][C:24]=3[N:23]([CH2:36][C:37]3[CH:38]=[CH:39][C:40]([C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=4[C:49]4[NH:3][C:4](=[O:7])[O:5][N:50]=4)=[CH:41][CH:42]=3)[C:22]2=[O:51])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 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-carbonitrile

Product 1

HCID 1360522863-(2-cyclohexyl-2-oxoethyl)-1-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 30%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of hydroxylammonium chloride (0.28 g), sodium hydrogencarbonate (0.43 g) and dimethyl sulfoxide (2.5 mL) was stirred at 50° C. for 30 min, 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 (0.29 g) was added, and the mixture was stirred at 90° C. for 20 hr. After allowing to cool to room temperature, ethyl acetate and water were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography and dissolved in tetrahydrofuran (2 mL). N,N′-Carbonyldiimidazole (0.061 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.056 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed successively with 1N hydrochloric acid and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound as a colorless amorphous solid (0.095 g, 30%).

Workup

  1. stirringthe mixture was stirred at 90° C. for 20 hr
  2. temperatureto cool to room temperature
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed successively with water and saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography
  8. dissolutiondissolved in tetrahydrofuran (2 mL)
  9. additionN,N′-Carbonyldiimidazole (0.061 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.056 mL) were added
  10. stirringthe mixture was stirred at room temperature for 2 hr
  11. additionThe reaction mixture was diluted with ethyl acetate
  12. washwashed successively with 1N hydrochloric acid and saturated brine
  13. dry with materialdried over anhydrous magnesium sulfate
  14. customThe solvent was evaporated under reduced pressure
  15. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-f1eaedb866fe48f8a67e92816f01fc92
Source dataset
uspto-grants-2013_08
Patent number
US08501750B2

Reaction notes

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