1,1'-Carbonyldiimidazole → 3-[4-(1,4-dioxaspiro[4.5]dec-8-yloxy)phenyl]-2-ethyl-5-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-6-propylpyrimidin-4(3H)-one

HRID 1674427Notes

Reaction equation

HRID 1674427 reaction equation
Cl.NO.[C:4](=[O:7])([O-])[OH:5].[Na+].[O:9]1[C:13]2([CH2:18][CH2:17][CH:16]([O:19][C:20]3[CH:25]=[CH:24][C:23]([N:26]4[C:31](=[O:32])[C:30]([CH2:33][C:34]5[CH:39]=[CH:38][C:37]([C:40]6[C:41]([C:46]#[N:47])=[CH:42][CH:43]=[CH:44][CH:45]=6)=[CH:36][CH:35]=5)=[C:29]([CH2:48][CH2:49][CH3:50])[N:28]=[C:27]4[CH2:51][CH3:52])=[CH:22][CH:21]=3)[CH2:15][CH2:14]2)[O:12][CH2:11][CH2:10]1.C(N1C=CN=C1)([N:55]1C=CN=C1)=O.N12CCCN=C1CCCCC2>CS(C)=O.C(OCC)(=O)C.O>[O:12]1[C:13]2([CH2:14][CH2:15][CH:16]([O:19][C:20]3[CH:25]=[CH:24][C:23]([N:26]4[C:31](=[O:32])[C:30]([CH2:33][C:34]5[CH:35]=[CH:36][C:37]([C:40]6[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=6[C:46]6[NH:55][C:4](=[O:7])[O:5][N:47]=6)=[CH:38][CH:39]=5)=[C:29]([CH2:48][CH2:49][CH3:50])[N:28]=[C:27]4[CH2:51][CH3:52])=[CH:22][CH:21]=3)[CH2:17][CH2:18]2)[O:9][CH2:10][CH2:11]1

Participants

9

Reactant 5

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 59469503HCID 59469503, compound

Product 1

HCID 1361467873-[4-(1,4-dioxaspiro[4.5]dec-8-yloxy)phenyl]-2-ethyl-5-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-6-propylpyrimidin-4(3H)-oneYield 64.3%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

A suspension of hydroxylamine hydrochloride (5.14 g) and sodium hydrogen carbonate (7.31 g) in dimethyl sulfoxide (30 mL) was stirred at 40° C. for 30 min, and then 4′-({1-[4-(1,4-dioxaspiro[4.5]dec-8-yloxy)phenyl]-2-ethyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl}methyl)biphenyl-2-carbonitrile (5.13 g) was added to the mixture, and the mixture was stirred at 90° C. for 12 hr. Water was added to the reaction mixture, and the precipitated solid was collected by filtration. The obtained solid was dissolved in ethyl acetate. The solution was washed with saturated brine and dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was dissolved in tetrahydrofuran (40 mL), and then 1,1′-carbonyldiimidazole (2.12 g, 13.1 mmol) and 1,8-diazabicyclo[5,4,0]undec-7-ene (2.0 mL, 13.1 mmol) were added thereto. The mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, and the mixture was successively washed with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel to give the title compound as a pale yellow amorphous solid (3.63 g, 64%).

Workup

  1. stirringthe mixture was stirred at 90° C. for 12 hr
  2. filtrationthe precipitated solid was collected by filtration
  3. dissolutionThe obtained solid was dissolved in ethyl acetate
  4. washThe solution was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was evaporated
  7. dissolutionThe residue was dissolved in tetrahydrofuran (40 mL)
  8. stirringThe mixture was stirred at room temperature for 2 hr
  9. washthe mixture was successively washed with water and saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-66287a34509640b495bcbc161be001f3
Source dataset
uspto-grants-2011_08
Patent number
US07998968B2

Reaction notes

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