Dimethyl Sulfoxide → 4-(1,4-dioxaspiro[4.5]dec-8-yl)-6-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-7-propyl-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-one

HRID 520163Notes

Reaction equation

HRID 520163 reaction equation
[Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[O:13]1[C:17]2([CH2:22][CH2:21][CH:20]([N:23]3[C:28](=[O:29])[C:27]([CH2:30][C:31]4[CH:36]=[CH:35][C:34]([C:37]5[C:38]([C:43]#[N:44])=[CH:39][CH:40]=[CH:41][CH:42]=5)=[CH:33][CH:32]=4)=[C:26]([CH2:45][CH2:46][CH3:47])[N:25]4[N:48]=[C:49]([C:51]([F:54])([F:53])[F:52])[N:50]=[C:24]34)[CH2:19][CH2:18]2)[O:16][CH2:15][CH2:14]1>C(OCC)(=O)C>[O:13]1[C:17]2([CH2:18][CH2:19][CH:20]([N:23]3[C:28](=[O:29])[C:27]([CH2:30][C:31]4[CH:32]=[CH:33][C:34]([C:37]5[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=5[C:43]5[NH:3][C:4](=[O:7])[O:5][N:44]=5)=[CH:35][CH:36]=4)=[C:26]([CH2:45][CH2:46][CH3:47])[N:25]4[N:48]=[C:49]([C:51]([F:54])([F:53])[F:52])[N:50]=[C:24]34)[CH2:21][CH2:22]2)[O:16][CH2:15][CH2:14]1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 670096644'-{[4-(1,4-Dioxaspiro[4.5]dec-8-yl)-5-oxo-7-propyl-2-(trifluoromethyl)-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile

Product 1

HCID 1360637324-(1,4-dioxaspiro[4.5]dec-8-yl)-6-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-7-propyl-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-one

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of hydroxylammonium chloride (396 mg), sodium hydrogen carbonate (638 mg) and dimethyl sulfoxide (3 mL) was stirred at 60° C. for 30 min, 4′-{[4-(1,4-dioxaspiro[4.5]dec-8-yl)-5-oxo-7-propyl-2-(trifluoromethyl)-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (220 mg) was added, and the mixture was stirred at 90° C. for 20 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (3 mL). N,N′-Carbonyldiimidazole (75 mg) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (70 mg) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous potassium hydrogensulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography [eluent: hexane/ethyl acetate=70/30→30/70 (volume ratio)] to give the title compound as a colorless amorphous compound (162 mg, 67%).

Workup

  1. stirringthe mixture was stirred at 90° C. for 20 hr
  2. washwashed with water
  3. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. dissolutionthe residue was dissolved in tetrahydrofuran (3 mL)
  6. additionN,N′-Carbonyldiimidazole (75 mg) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (70 mg) were added
  7. stirringthe mixture was stirred at room temperature for 2 hr
  8. additionThe reaction mixture was diluted with ethyl acetate
  9. washwashed with saturated aqueous potassium hydrogensulfate solution
  10. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  11. customThe solvent was evaporated under reduced pressure
  12. customthe residue was purified by silica gel chromatography [eluent: hexane/ethyl acetate=70/30→30/70 (volume ratio)]

Sources & evidence

ORD record
ord-8ff03a05b4754d2e9c77eeac0359bc5a
Source dataset
uspto-grants-2015_08
Patent number
US09115136B2

Reaction notes

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