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

HRID 1889576Notes

Reaction equation

HRID 1889576 reaction equation
[Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[CH:13]1([C:19](=[O:49])[CH2:20][N:21]2[C:26](=[O:27])[C:25]3[CH:28]=[C:29]([CH2:31][CH3:32])[S:30][C:24]=3[N:23]([CH2:33][C:34]3[CH:39]=[CH:38][C:37]([C:40]4[C:41]([C:46]#[N:47])=[CH:42][CH:43]=[CH:44][CH:45]=4)=[CH:36][CH:35]=3)[C:22]2=[O:48])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1>C(Cl)(Cl)Cl>[CH:13]1([C:19](=[O:49])[CH2:20][N:21]2[C:26](=[O:27])[C:25]3[CH:28]=[C:29]([CH2:31][CH3:32])[S:30][C:24]=3[N:23]([CH2:33][C:34]3[CH:35]=[CH:36][C:37]([C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=4[C:46]4[NH:3][C:4](=[O:7])[O:5][N:47]=4)=[CH:38][CH:39]=3)[C:22]2=[O:48])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 593516544'-{[3-(2-cyclohexyl-2-oxoethyl)-6-ethyl-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}biphenyl-2-carbonitrile

Product 1

HCID 1360522993-(2-cyclohexyl-2-oxoethyl)-6-ethyl-1-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}thieno[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 76.3%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of hydroxylammonium chloride (0.91 g), sodium hydrogencarbonate (1.3 g) and dimethyl sulfoxide (13 mL) was stirred at 40° C. for 30 min, 4′-{[3-(2-cyclohexyl-2-oxoethyl)-6-ethyl-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}biphenyl-2-carbonitrile (0.67 g) was added, and the mixture was stirred at 90° C. for 16 hr. The reaction mixture was diluted with chloroform, 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 methylene chloride (20 mL). N,N′-Carbonyldiimidazole (0.32 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.29 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with chloroform, washed successively with saturated aqueous potassium hydrogensulfate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by preparative HPLC to give the title compound as colorless crystals (0.57 g, 76%).

Workup

  1. stirringthe mixture was stirred at 90° C. for 16 hr
  2. washwashed successively with water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography
  6. dissolutiondissolved in methylene chloride (20 mL)
  7. additionN,N′-Carbonyldiimidazole (0.32 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.29 mL) were added
  8. stirringthe mixture was stirred at room temperature for 2 hr
  9. additionThe reaction mixture was diluted with chloroform
  10. washwashed successively with saturated aqueous potassium hydrogensulfate solution and saturated brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customThe solvent was evaporated under reduced pressure
  13. customThe obtained residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-e6145dae252f474f9278a4bcea31fd65
Source dataset
uspto-grants-2013_08
Patent number
US08501750B2

Reaction notes

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